Folia Pharmaceutica Universitatis Carolinae: LII

COVER
UNIVERSITAS CAROLINA PRAGENSIS
FOLIA
PHARMACEUTICA
UNIVERSITATIS
CAROLINAE
ISSN 1210-9495
FOLIA PHARMACEUTICA UNIVERSITATIS CAROLINAE
LII
LII
Folia_LII_obalka.indd 1Folia_LII_obalka.indd 1 05.03.2026 15:1805.03.2026 15:18
FOLIA PHARMACEUTICA UNIVERSITATIS CAROLINAE
LII
A anged by Assoc. P o . RND . Ve onika Ople alo á, Ph.D.
Lec u ed: Assoc. P o . RND . Vě a Klimešo á, CSc.,
Assoc. P o . Pha mD . Jakub Chlebek, Ph D.
Edi o ial Ad iso y Boa d: Assoc. P o . RND . Pa el Doležal, CSc.,
P o . Pha mD . Ma in Doležal, Ph.D., P o . MUD . Ja osla D ša a, CSc.,
P o . MUD . Radomí H dina, CSc., P o . RND . Lubomí Ople al, CSc.,
Assoc. P o . RND . Ve onika Ople alo á, Ph.D., Assoc. P o . RND . Mi osla Polášek, CSc.,
P o . RND . Jiří Vlček, CSc., Assoc. P o . RND . Pa la Žáčko á, CSc.,
Assoc. P o . RND . Ve onika Ople alo á, Ph.D. (edi o )
Published by Cha les Uni e si y
Ka olinum P ess
P ague 2026
Typese by Ka olinum P ess
© Cha les Uni e si y, 2026
ISSN 1210-9495
ISBN 978-80-246-6152-0
ISBN 978-80-246-6164-3 (pd )
h ps://doi.o g/10.14712/9788024661643
Cha les Uni e si y
Ka olinum P ess
www.ka olinum.cz
[email p o ec ed]
CONTENTS
Abs ac s . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 7
11 h Pos g adua e and Pos doc Con e ence o he Facul y o Pha macy
in H adec K álo é, Cha les Uni e si y, H adec K álo é, 27–28 Janua y 2021 . . . . . . . . . . . . . 7
Bioo ganic and Pha maceu ical Chemis y Sec ion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 7
Pha macognosy and Toxicology o Na u al P oduc s Sec ion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 27
Pha maceu ical Technology Sec ion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 41
Pha maceu ical Analysis and Bioanaly ical Chemis y Sec ion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 51
Clinical and Social Pha macy Sec ion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 95
28 h Na ional S uden s’ Scien i ic Con e ence o he Facul y o Pha macy
in H adec K álo é, Cha les Uni e si y, H adec K álo é, 13 Ap il 2021 [online] . . . . . . . . . . 107
Sec ion o Biological Sciences . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 107
Sec ion o Chemical Sciences . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 122
Sec ion o Pha maceu ical Technology . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 137
Sec ion o Social and Clinical Pha macy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 145
Bibliog aphy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 151
Publica ions o he Facul y o Pha macy in H adec K álo é, Cha les Uni e si y in he Yea 2021 . . . . . . . . 151
O iginal Pape s and Re iews . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 151
Mul icen e S udies . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 162
A icles in Jou nals wi hou Impac Fac o and P oceedings . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 163
Monog aphies and Tex books . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 164
Pa en s . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 165
Deg ees . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 165
Social Happenings . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 175
In Memo y o Assoc . P o . RND . Pe Kleme a, CSc . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 175
Ins uc ions o Au ho s . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 176
CONTENTS

7
2026 Folia Pha m . Uni . Ca ol . LII Pag . 7–106
ABSTRACTS
11 h POSTGRADUATE AND POSTDOC CONFERENCE
OF THE FACULTY OF PHARMACY IN HRADEC KRÁLOVÉ,
CHARLES UNIVERSITY,
HRADEC KRÁLOVÉ, 27–28 JANUARY 2021
BIOORGANIC AND PHARMACEUTICAL CHEMISTRY SECTION
SUPRAMOLECULAR INTERACTION OF TETRAPYRAZINO-PORPHYRAZINES
DEMUTH, J., NOVÁKOVÁ, V., ZIMČÍK, P.
Depa men o Pha maceu ical Chemis y and Pha maceu ical Analysis, Facul y o Pha macy
in H adec K álo é, Cha les Uni e si y, Czech Republic
e-mail: demu hj1@ a .cuni .cz
Te apy azinopo phy azines (TPyzPzs), membe s o he ph halocyanine amily, a e
syn he ic plana mac omolecules . TPyzPzs ha e ema kable spec al p ope ies due o
hei sys em o a oma ic double bonds . These mac omolecules can abso b ligh be ween
300–700 nm, and a e wa d, hey could elease he abso bed ene gy by emi ing luo es-
cence . Alkylamino subs i u ed TPyzPzs a e an in e es ing sub ype o TPyzPzs, changing
hei spec al p ope ies due o sup amolecula in e ac ion . The sup amolecula in e ac ion
lays in s acking wo molecules o each o he – J-dime o ma ion (Fig . 1) . The mono-
Fig. 1
Fig. 1. J- ype o agg ega e
8
me ic alkylamino TPyzPzs ha e only weak luo escence because he as elaxing p ocess
quenches i .1 On he o he hand, dime ic alkylamino TPyzPzs ha e good luo escence wi h
a signi ican ba hmo opic shi . Agg ega es could be dissol ed by he addi ion o coo -
dina ion sol en (e.g ., py idine, N-me hylimidazole), which caused changes in abso p ion
spec a (Fig . 2) .2 This p ojec s udied he backg ound o possible u he applica ion o
alkylamino TPyzPzs .
The s udy was suppo ed by he Czech Science Founda ion (P ojec No. 17-19094S),
by he G an Agency o Cha les Uni e si y (P ojec No. 1168217) and om he p ojec o
Speci ic Academic Resea ch (SVV 260 547).
Re e ences
1. NOVÁKOVÁ, V., ZIMČÍK, P., MILETÍN, M. e al .: Phys . Chem . Chem . Phys ., 12, 2010, 2555–2563 .
2. DEMUTH, J., MILETÍN, M., MACHAN, M. e al .: ChemPlusChem, 85, 2020, 527–537 .
ANIONIC VERSUS CATIONIC PHTHALOCYANINES FOR PHOTODYNAMIC
THERAPY: WHAT A DIFFERENCE THE CHARGE MAKES
KOLLÁR, J .,1 MACHÁČEK, M.,2 HALAŠKOVÁ, M .,2 DEMUTH, J .,1 ROHLÍČKOVÁ, M.,2
NOVÁKOVÁ, V .,1 ZIMČÍK, P.1
1 Depa men o Pha maceu ical Chemis y and Pha maceu ical Analysis, Facul y o Pha macy
in H adec K álo é, Cha les Uni e si y, Czech Republic
2 Depa men o Biochemical Sciences, Facul y o Pha macy in H adec K álo é, Cha les Uni e si y,
Czech Republic
e-mail: kolla j@ a .cuni .cz
Ph halocyanines (Pcs) and hei aza-analogues ep esen a p omising g oup o o ganic
dyes wi h in e es ing pho ophysical p ope ies (s ong abso p ion in a ea o e 600 nm and
s ong single oxygen p oduc ion) highly sui able o he use in pho odynamic he apy o
cance . The li e a u e epo s on ca ionic and anionic Pcs o pho odynamic he apy sugges
sys ema ically signi ican di e ences in hei pho odynamic ac i i y.
Fig. 2
Fig. 2. Changes in he abso p ion spec a
9
This p ojec was ocused on he se ies o anionic and ca ionic zinc(II) Pcs and in es i-
ga ed hei pho ophysical, physicochemical, binding and biological p ope ies wi h he aim
o inding he pa ame e s and/o ac o s ha may con ibu e o he subs an ial di e ence in
pho odynamic ac i i y be ween Pcs bea ing opposi e cha ges on pe iphe al subs i uen s .
Fou di e en se s o compounds we e in oduced in o he s udy, namely anionic hyd o-
philic, ca ionic hyd ophilic, anionic amphiphilic and ca ionic amphiphilic o compa e bo h
he in luence o he cha ge ype and i s dis ibu ion on he mac ocycle co e. All Pcs we e
es ed on pho odynamic ac i i y in i o on HeLa cells wi h di e en ac i i y o anionic
Pcs (EC50 ~ 0.3–10 μM) and ca ionic Pcs (EC50 ~ 3–50 nM) . The e ec o pH, binding o
se um p o eins, in e ac ion wi h biomemb anes, subcellula localiza ion and elocaliza ion
a e i adia ion we e disclosed o be he main ac o s esponsible o lowe pho oac i i y
o anionic Pcs .1
The wo k was suppo ed by he Czech Science Founda ion (P ojec No. 19-14758Y),
by he Cha les Uni e si y P ojec PRIMUS/20/SCI/013 and om he p ojec o Speci ic
Academic Resea ch (SVV 260 547).
Re e ences
1. KOLLÁR, J., MACHÁČEK, M., HALAŠKOVÁ, M . e al.: J. Med. Chem., 63, 2020, 7616−7632.
PREPARATION OF NEW MELTING TEMPERATURE MODIFIERS
KOSTELANSKÝ, F., HAVLÍNOVÁ, Z., MILETÍN, M., ZIMČÍK, P.
Depa men o Pha maceu ical Chemis y and Pha maceu ical Analysis, Facul y o Pha macy
in H adec K álo é, Cha les Uni e si y, Czech Republic
e-mail: kos ela @ a .cuni .cz
Mel ing empe a u e di e ence (ΔTm) be ween complemen a y and misma ched
duplex has a c ucial ole o disc imina ion o poin mu a ions o single nucleo ide poly-
mo phisms. The ΔTm is dec easing wi h he leng h o oligodeoxynucleo ide. F om his
poin o iew, sho e oligodeoxynucleo ide p obes a e ad an ageous due o highe ΔTm
compa ed wi h longe p obes . On he o he hand, hei low mel ing empe a u e is he
main disad an age. Mel ing empe a u e modi ie s a e used o elimina ion o he disad-
an age. The e a e h ee ypes o modi ie s ha can be used o he mal s abilisa ion o
oligodeoxynucleo ide duplexes: polyamines1, mino g oo e binde s2 and in e cala o s .3
In ou wo k we ocused on p epa a ion o new ac idine de i a i es . They we e p epa ed
by modi ied published p ocedu es. Ou ac idine de i a i es we e es ed in solu ion and
compa ed o he polyamine (spe mine) and well known MGB Hoechs 33258 . Majo i y
o ac idine de i a i es showed compa able o be e ac i i y in solu ion han spe mine o
Hoechs 33258 . Two mos p omising ac idine de i a i es we e selec ed and co alen ly
a ached o he oligodeoxynucleo ide p obe by click chemis y . P obes we e es ed a PCR
condi ions .
16
The s udy was suppo ed by he Czech Science Founda ion (P ojec No. 18-17868S),
by he G an Agency o Cha les Uni e si y (P ojec No. 205007) and om he p ojec o
Speci ic Academic Resea ch (SVV 260 547).
Re e ences
1. BRŮŽA, Z., KRATOCHVÍL, J., POUR, M. e al .: Chem .– Eu . J ., 25, 2019, 8053–8060 .
2. CHEN, S ., LIU, Y ., LIU, Z . e al .: RSC Ad ., 6, 2016, 26412–26420 .
3. FURUTA, T ., FUKUYAMA, Y ., ASAKAWA, Y .: Phy ochemis y, 25, 1986, 517–520 .
MICHAEL AND ANTI-MICHAEL ADDITIONS TO [3]DENDRALENES
PERDOMO, S . M ., ANTAL, R ., POUR, M .
Depa men o O ganic and Bioo ganic Chemis y, Facul y o Pha macy in H adec K álo é,
Cha les Uni e si y, Czech Republic
e-mail: pe domos@ a .cuni .cz
Dend alenes a e acyclic c oss-conjuga ed polyenes wi h an in e es ing, as ye unexam-
ined eac i i y and high po en ial o u he syn he ic applica ions .1 Ou esea ch g oup
de eloped a no el syn hesis o a iously subs i u ed elec on-poo [3]dend alenes wi h
a dis inc dissonan cha ac e , and disco e ed an unexpec ed beha iou o hese com-
pounds upon nucleophilic a ack .
In iew o he p elimina y esul s and assuming ha elimina ion o he dissonan na u e
was he d i ing o ce o hese ans o ma ions, we u he ocused on a ious e sions o
Michael addi ions o dend alenic s uc u es . In some cases, an i-Michael addi ions also oc-
cu ed . Using mild condi ions and di e en combina ions o nucleophiles and dend alenes,
cycliza ions and/o simple addi ions ha e been obse ed.
This s udy was suppo ed by he Czech Science Founda ion (P ojec No. 18-17868S),
by he G an Agency o Cha les Uni e si y (P ojec No. 1348119) and om he p ojec o
Speci ic Academic Resea ch (SVV 260 547).
Re e ences
1. HOPF, H ., SHERBURN, M . S .: Angew . Chem . In . Ed ., 51, 2012, 2298–2338 .
Scheme 1. Syn hesis o he i le compounds

17
STUDY OF 2,5-DISUBSTITUTED 1,3,4-OXADIAZOLES AS POTENTIAL
ANTITUBERCULOTICS
PFLÉGR, V ., KRÁTKÝ, M ., VINŠOVÁ, J .
Depa men o O ganic and Bioo ganic Chemis y, Facul y o Pha macy in H adec K álo é,
Cha les Uni e si y, Czech Republic
e-mail: [email p o ec ed]
Nowadays, small he e ocyclic molecules (e.g., oxadiazoles, e azole, iazoles) ha e
been s udied as po en ial an i ube culo ics . Compounds wi h his s uc u al mo i a ge
M. ube culosis (M b .), including esis an s ains .1 We ha e p epa ed a se ies o 2,5-dis-
ubs i u ed 1,3,4-oxadiazoles wi h e y p omising ac i i y agains se e al mycobac e ial
s ains . Asymme ic 1,2-diacylhyd azides we e p epa ed by he eac ion o monosubs i-
u ed comme cially a ailable o in-house p epa ed (acyl) hyd azine wi h a app op ia e
acyl chlo ide in he p esence o a base using anhyd ous e ahyd o u an (THF) as he
sol en . 2,5-Disubs i u ed oxadiazoles we e ob ained di ec ly by dehyd a i e cycliza ion
o 1,2-diacylhyd azides (Scheme 1) . In gene al, he syn heses ga e sa is ac o y yields .
The compounds we e e alua ed o hei in i o an imycobac e ial ac i i y agains d ug-
suscep ible M b H37R and non ube culous mycobac e ia (NTM, M. a ium, M. kansasii) .
De e mining he ac i i y agains mul id ug- esis an M b . as well as selec i i y index a e
unde in es iga ion . No ac i i y agains G am-posi i e and G am-nega i e bac e ia as well
as ungal pa hogens was iden i ied.
The s udy was suppo ed by he Czech Science Founda ion (P ojec . No. 20-19638Y)
and om he p ojec o Speci ic Academic Resea ch (SVV 260 547).
Re e ences
VOSÁTKA, R ., KRÁTKÝ, M ., ŠVARCOVÁ, M . e al .: Eu . J . Med . Chem ., 151, 2018, 824–835 .
Fig. 11
Scheme 1. Addi ions o nucleophiles o [3]dend alenes
18
SYNTHESIS OF OMEGA-HYDROXYLATED CERAMIDES USING OLEFINATION
REACTIONS
ONDREJČEKOVÁ, V., OPÁLKA, L., VÁVROVÁ, K.
Depa men o O ganic and Bioo ganic Chemis y, Facul y o Pha macy in H adec K álo é,
Cha les Uni e si y, Czech Republic
e-mail: somme o @ a .cuni .cz
Omega-hyd oxyla ed ce amides (O-Ce ) belong o a subclass o Ce wi h ul along
N-acyl chains . Toge he wi h o he g oups o Ce , ee a y acids and choles e ol, hese
lipids c ea e mul ilamella s uc u es in s a um co neum, which a e esponsible o skin
ba ie unc ion . O-Ce occu in wo o ms: ee o m o bound o he su ace o co neo-
cy es whe e hey o m a co neocy e lipid en elope (Fig . 1) . The de ailed ole o co alen ly
bound O-Ce emains unclea .
Fig. 12
Scheme 1. Syn hesis o he i le compounds
HO
R
OH
HN
O
O
R = H F ee ce amide
R = Co neocy e Co alen ly bound ce amide
Ce amide OS
O
Fig. 1. S uc u e o ee O-Ce and O-Ce co alen ly bound o he co neocy e
The main objec i e o his p ojec was o op imize he syn he ic p ocedu e owa ds
h ee subclasses o O-Ce , speci ically Ce OS, OP and OdS.
Comple e syn hesis o O-Ce has no been epo ed ye . In his p ojec , we modi ied
a p e iously published p ocedu e o ul along Ce syn hesis whe e we ocused on an
imp o emen o he mos complica ed s eps o his syn hesis . P o ec ed 16-hyd oxyhexa-
decanal as a c ucial componen o ole ina ion eac ions was p epa ed in ou s eps om
hexadecanolide wi h high yield . This aldehyde was hen connec ed wi h a ious he e o-
cyclic sul ones using ole ina ion eac ions, such as Julia and Julia-Kocienski eac ions
o ob ain a p o ec ed 32-hyd oxydo iacon enoic acid, which is an O-Ce p ecu so . This
change in eac ion p ocedu e led o a signi ican imp o emen in he eac ion yield and o
a dec ease in cos s o s a ing ma e ials .
19
The s udy was suppo ed by he Czech Science Founda ion (P ojec No. 19-09135J),
by he G an Agency o Cha les Uni e si y (P ojec No. 1194119) and om he p ojec o
Speci ic Academic Resea ch (SVV 260 547).
LIPID-DECORATED DENDRIMERS FOR STUDYING THE BEHAVIOR
OF CORNEOCYTE LIPID ENVELOPE
VELISSARI, P .,1 PARASKEVOPOULOS, G .,2 VÁVROVÁ, K .1
1 Depa men o O ganic and Bioo ganic Chemis y, Facul y o Pha macy in H adec K álo é,
Cha les Uni e si y, Czech Republic
2 Depa men o Pha maceu ical Technology, Facul y o Pha macy in H adec K álo é,
Cha les Uni e si y, Czech Republic
e-mail: elissap@ a .cuni .cz
Skin is he bigges o gan in he human body and p o ec s i om excessi e wa e loss
while hampe s he en ance o undesi ed subs ances, alle gens and mic obes . Skin’s ou e -
mos laye , s a um co neum (SC), holds he p incipal skin ba ie and consis s o la ened
dead cells, known as co neocy es, embedded in a hyd ophobic lipidic ma ix . Co alen ly
a ached o co neocy e’s su ace a e ce amides o ming he so-called “co neocy e lipid
en elope” (CLE) .1 Mos biophysical SC models a e aking in o conside a ion only he
lipidic ma ix . In ou app oach, we a e ocusing on he de elopmen o co neocy e mim-
icking compounds o c ea e a mo e complex SC model ha would inco po a e hyd ophilic
co neocy e mimicking en i ies wi h/wi hou CLE in he lipidic ma ix o s udy he pu-
a i e sca olding ole o CLE . Fo his pu pose, we plan o deco a e ou h gene a ion
PAMAM dend ime s wi h ce amides . Fo he de elopmen o an e ec i e syn he ic p o-
ocol, PAMAM dend ime s and ce amides we e no used di ec ly bu we e eplaced by
in-house syn hesized dend ime s and long-chain alipha ic alcohols wi h a e minal iple
bond, espec i ely . A coppe -ca alyzed azide-alkyne cycloaddi ion p o ocol was de eloped
o couple he modi ied dend ime s wi h he ce amide mimicking compound. The syn he ic
p o ocol has al eady been es ablished and will be applied o conjuga e he PAMAM den-
d ime s wi h he ce amides .
The s udy was suppo ed by he Czech Science Founda ion (P ojec No. 19-09135J) and
om he p ojec o Speci ic Academic Resea ch (SVV 260 547).
Re e ences
1. VÁVROVÁ, K., KOVÁČIK, A., OPÁLKA, L.: Eu . Pha m. J., 64, 2017, 28–35.
20
DESIGN, SYNTHESIS AND BIOLOGICAL EVALUATION
OF 3-AMINOPYRAZINE-2-CARBOXAMIDE DERIVATIVES
AS POTENTIAL ANTIMICROBIALS
PALLABOTHULA, V . S . K ., ZITKO, J .
Depa men o Pha maceu ical Chemis y and Pha maceu ical Analysis, Facul y o Pha macy
in H adec K álo é, Cha les Uni e si y, Czech Republic
e-mail: pallabo @ a .cuni .cz
Tube culosis (TB) emains among he WHO op 10 causes o dea h despi e a ailable
ea men s1 and BCG accine. As pa o ou ongoing esea ch on py azinamide (a i s -line
an i ube cula ) de i a i es, we epo he design and syn hesis o no el 3-aminopy azine-
2-ca boxamide de i a i es along wi h hei biological e alua ion . Almos 50 compounds
we e p epa ed acco ding o Scheme 1 and e alua ed o hei in i o ac i i y agains
a ious s ains o mycobac e ia and o he s ains o pa hogenic bac e ia and ungi . The
ac i e compounds we e only om se ies-1 (R is a subs i u ed phenyl) . The mos ac i e
compounds we selec i e owa ds inhibi ion o M b H37Ra and M b H37R (o e o he
mycobac e ial s ains) and exe ed MIC (Minimum Inhibi o y Concen a ion) anging om
1 .98 o 7 .81 µg mL‒1. The inal compounds we e also s udied o cy o oxici y on HepG2
cell line ollowed by SAR . Ti le compounds will also be s udied as po en ial inhibi o s o
(human) p olyl- RNA syn he ase based on hei s uc u al simila i ies o con i med inhibi-
o s epo ed in he li e a u e .2
Fig. 14
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Scheme 1. Syn hesis o inal compounds
a: acyl chlo ides/py idine/A medium, b: 2M ammonia in E OH
The s udy was suppo ed by he Czech Science Founda ion (P ojec No. 20-19638Y)
and om he p ojec o Speci ic Academic Resea ch (SVV 260 547).
Re e ences
1. Wo ld Heal h O ganiza ion, Global Tube culosis Repo 2020 h ps://www.who.in /publica ions/i
/i em/9789240013131
2. ADACHI, R ., OKADA, K ., SKENE, R . e al .: Biochem . Biophys . Res . Commun ., 488, 2017, 393–399 .
21
INSECT MODEL, GALLERIA MELLONELLA, AS NEW POWERFUL TOOL
FOR THE DRUG DISCOVERY RESEARCH
KONEČNÁ, K., DIEPOLTOVÁ, A., JANĎOUREK, O., ZÁVESKÁ, V.
Depa men o Biological and Medical Sciences, Facul y o Pha macy in H adec K álo é,
Cha les Uni e si y, Czech Republic
e-mail: konecna@ a .cuni .cz
The inal and o en c ucial phase o d ug disco e y esea ch in ol es he using o ap-
p op ia e animal models . Mice and a s a e he mos equen ly chosen models o his
pu pose. Howe e , in aking in o accoun 3Rs (Replacemen , Reduc ion, and Re inemen )
c i e ia, which a e conside ed o be a amewo k o conduc ing high-quali y science in he
academic sec o , i is desi able o look o a sui able al e na i e app oach .1
Galle ia mellonella ep esen s an insec animal model enjoying inc easing popula i y in
esea ch communi ies . This animal model is employed in s udies ocused on mechanisms
o mic obial pa hogenesis and i ulence, in disc imina ion be ween in i o high and non/
low- oxici y, o in he s udy o in i o e icacy o candida e an i-in ec i e d ugs. This
model’s undeniable p os a e ha e hical app o al is no needed, inancial cos s a e sig-
ni ican ly lowe han he mouse o a model, and no special lab equipmen is equi ed.2,3
We a e cu en ly expe ienced in his animal model ea ing and i s use o in i o oxici y
es ing . Op imiza ion o he me hodical app oaches o in i o candida e an i-in ec i e d ug
e icacy es ing and in i o mic obial bio ilm o ma ion is now in he p ocess.
The s udy was suppo ed by he Czech Science Founda ion (P ojec No. 20-19638Y)
and om he p ojec o Speci ic Academic Resea ch (SVV 260 549).
Re e ences
1. IGNASIAK, K ., MAXWELL, A .: BMC Res . No es, 10, 2017, 428 .
2. TSAI, C . J ., LOH, J . M ., PROFT, T.: Vi ulence, 7, 2016, 1705‒1711.
3. ALLEGRA, E ., TITBALL, R . W ., CARTER, J . e al .: Chemosphe e, 198, 2018, 469–472 .
STUDY OF BOOSTER EFFECT OF COMPOUNDS IN COMBINATION
WITH STANDARD DRUGS USED IN THERAPY OF TUBERCULOSIS
JANĎOUREK, O., KONEČNÁ, K., DIEPOLTOVÁ, A.
Depa men o Biological and Medical Sciences, Facul y o Pha macy in H adec K álo é,
Cha les Uni e si y, Czech Republic
e-mail: jando6aa@ a .cuni .cz
Tube culosis is s ill one o he mos h ea ening heal h p oblems all o e he wo ld .
Al hough he absolu e numbe s o new cases a e dec easing, p oblem has a isen wi h e-
sis an s ains o Mycobac e ium ube culosis, which is he causa i e agen o ube culosis .
These cases a e ha d o cu e and i is necessa y o use second line d ugs . This ea men is
expensi e, ime consuming and he isk o side e ec s is high .

22
T ea men o ube culosis is always based on combina ion o a leas 2 o 4 d ugs ac-
co ding o he apy egimen . Using combina ions can be e y use ul as well as icky .
Combina ions can imp o e he e ec and lowe he isk o esis ance de elopmen . On he
o he hand, hese combina ions mean highe isk o in e ac ions ha can esul in an ago-
nis ic e ec s o hese molecules . Ou come o hose ac o s is ailu e o he apy ha can
lead o signi ican sp eading o in ec ion and highe mo ali y a e.
Syn hesis o no el compounds is one o he mos impo an s eps o ube culosis
e adica ion. Bu he chance o ind molecule wi h no el mechanism o ac ion, o which
mycobac e ia will no be able o e ol e esis ance, is qui e low . So, one oppo uni y o
slow down he sp eading is o s udy in e ac ions be ween d ugs used o ea men and
new molecules .
One o he me hods o s udy hese in e ac ions is called checke boa d assay . I is based
on s udying combina ions o wo compounds in a ious concen a ions a ec ing he esul .
The e a e 4 possible in e ac ions exp essed as FIC (F ac ional Inhibi o y Concen a ion),
namely An agonism, Indi e ence, Addi i i y, Syne gism . Las h ee named ca ego ies a e
op imal o p ac ice, bu syne gism is he mos desi ed . Me hodology o an imycobac e ial
checke boa d assay was op imized in his wo k .
The s udy was suppo ed by he Czech Science Founda ion (P ojec No. 20-19638Y),
by Resea ch p og amme De elopmen and S udy o D ugs (P og ess Q42) and om he
p ojec o Speci ic Academic Resea ch (SVV 260 547).
TOWARDS TO IN VITRO ANTIBIOFILM ACTIVITY SCREENING –
INTRODUCTION OF APPROPRIATE METHODICAL APPROACH
FOR STAPHYLOCOCCAL BIOFILM FORMATION
DIEPOLTOVÁ, A., KONEČNÁ, K., JANĎOUREK, O., NACHTIGAL, P.
Depa men o Biological and Medical Sciences, Facul y o Pha macy in H adec K álo é,
Cha les Uni e si y, Czech Republic
e-mail: diepol a@ a .cuni .cz
S aphylococcus au eus (SA) and S aphylococcus epide midis (SE) a e he mos com-
mon pa hogens om he genus S aphylococcus, causing bio ilm-associa ed in ec ions.
Bac e ia in bio ilms a e di icul o e adica e due o hei esis ance and se e as a ese -
oi o ecu ing pe sis en in ec ions .1 A a ie y o p o ocols o in i o d ug ac i i y
es ing agains s aphylococcal bio ilms has been in oduced. Howe e , he e a e o en
undamen al di e ences . In ou p elimina y s udy, we de eloped op imal condi ions o
s aphylococcal bio ilm o ma ion on plas ic pegs in o de o se a me hodology o he
e alua ion o he an ibio ilm ac i i y o candida e molecules. The con enience o he
plas ic pegs lies in hei emo abili y om he lid o easy access o mul iple equi a-
len bio ilms, and in possibili y o in si u de ec ion and quan i ica ion by con ocal lase
mic oscopy. Fo he pu pose o enhancemen in s aphylococcal bio ilm o ma ion, he im-
pac o peg su ace modi ica ion wi h 3 di e en coa ing ma e ials was s udied as well. An
inc ease o bio ilm biomass was e alua ed by c ys al iole s aining me hod.2 The basic
23
p econdi ion o ob aining ele an and ep oducible da a ega ding an ibio ilm ac i i y is
he o ma ion o obus bio ilms wi h ypical a ibu es such as he p esence o a bio ilm
ma ix . In ou s udy, in i o condi ions e ealed ha we ully me he p econdi ions o
he SA and me hicillin- esis an SA s ains . In conclusion, we demons a ed s a is ically
signi ican enhancemen o bio ilm o ma ion in all s udied s aphylococcal s ains, includ-
ing ei he s ong bio ilm p oduce pheno ype (SA, me hicillin- esis an SA) and weak
bio ilm p oduce pheno ype (SE).
The s udy was suppo ed by he Czech Science Founda ion (P ojec No. 20-19638Y),
and om he p ojec o Speci ic Academic Resea ch (SVV 260 549).
Re e ences
1. DONLAN, R . M .: Eme g . In ec . Dis ., 8, 2002, 881–890 .
2. CHRISTENSEN, G . D ., BALDASSARRI, L ., SIMPSON, W . A .: Me hods Enzymol . 253, 1995, 477–500 .
DERIVATIVES OF QUINOXALINE-2-CARBOXAMIDES AS POTENTIAL
ANTIMYCOBACTERIALS
BOUZ, G., BOUZ, S., ZITKO, J., DOLEŽAL, M.
Depa men o Pha maceu ical Chemis y and Pha maceu ical Analysis, Facul y o Pha macy
in H adec K álo é, Cha les Uni e si y, Czech Republic
e-mail: bouzg@ a .cuni .cz
Despi e he es ablished ea men s, ube culosis emains an ala ming h ea o public
heal h acco ding o WHO .1 No el agen s a e needed o o e come he inc easing a es o
esis ance and pe haps achie e e adica ion . As pa o ou long- e m esea ch on py azine
de i a i es, we p epa ed a se ies o N-subs i u ed quinoxaline-2-ca boxamides (Fig . 1)
and e alua ed hei in i o an i ube cula ac i i y . Se e al quinoxaline de i a i es we e
ound in he li e a u e o possess an i ube cula ac i i y .2 Quinoxaline-2-ca boxylic acid
was ac i a ed by oxalyl chlo ide and eac ed wi h di e en anilines o benzylamines
in he p esence o py idine a oom empe a u e, o e nigh wi h s i ing, and ob ained
c udes we e hen pu i ied wi h lash ch oma og aphy. In addi ion o ac i i y assessmen ,
inal compounds we e sc eened o hei in i o cy o oxici y on HepG2 li e cance
cell lines . In i o ac i i y agains M b H37Ra ( ep esen ed by MIC) anged be ween
3 .91–500 µg mL−1, wi h mos compounds ha ing mode a e o good ac i i ies (MIC <
15 .625 µg mL−1) .
Fig. 15
Fig. 15
Fig. 1. S uc u es o he s udied compounds
24
This wo k was suppo ed by EFSA-CDN (Reg. No. CZ.02.1.01/0.0/0.0/16_019/00008
41) co- unded by ERDF, by he Czech Science Founda ion (P ojec No. 20-19638Y) and
om he p ojec o Speci ic Academic Resea ch (SVV 260 547).
Re e ences
1. Wo ld Heal h O ganiza ion, Global Tube culosis Repo 2020. h ps://www.who.in /publica ions/i/i em
/9789240013131
2. PERAMAN, R ., KUPPUSAMY, R ., KILLI, S . K . e al .: In . J . Med . Chem ., 2016, a . 6471352 .
PYRAZINE-2-CARBOHYDRAZIDE DERIVATIVES AS POTENTIAL
ANTIITUBERCULARS
NAWROT, D., ZITKO, J., DOLEŽAL, M.
Depa men o Pha maceu ical Chemis y and Pha maceu ical Analysis, Facul y o Pha macy
in H adec K álo é, Cha les Uni e si y, Czech Republic
e-mail: naw o d@ a .cuni .cz
Tube culosis, an in ec ious disease, is a majo p oblem when i comes o numbe o
casual ies and g owing an imic obial esis ance .1 I is ea ed by i s -line d ugs (e.g .,
py azinamide), bu new agen s a e needed .
In 2014, Rod igues e al .2 es ed a se ies o py azine-2-ca bohyd azide de i a i es as
po en ial an icance class . Compounds we e es ed on h ee di e en umo cell lines and
hei g ow h inhibi ion was no sa is ac o y o de elop such compounds as new an ican-
ce agen s . This wo k inspi ed us o he de elopmen ou i le se ies and e alua e hei
an imic obial ac i i y . Cu en se ies is based on py azine-2-ca bohyd azide ha is bound
o di e en he e ocycles by imine bond (example o compound: N-benzylidenepy azine-
2-ca bohyd azide) ha will be u he de i a ized in o disubs i u ed compounds (example
N-benzoyl-N′-benzylidenepy azine-2-ca bohyd azide). Compounds we e es ed o bio-
logical ac i i y agains selec ed s ains o Mycobac e ium, eigh ungi s ains and eigh
bac e ial s ains . The minimum inhibi o y concen a ion (MIC) o es ed mycobac e ial
s ains was de e mined o all es ed compounds beside isoniazid, cip o loxacin and i-
ampicin as e e ence s anda d d ugs . Resul s o he biological es ing and s uc u e ac i i y
ela ionships a e discussed in he p esen a ion .
The s udy was suppo ed om he p ojec o Speci ic Academic Resea ch (SVV 260 547).
Re e ences
1. Wo ld Heal h O ganiza ion: Global Tube culosis Repo 2020. h ps://www.who.in /publica ions/i/i em
/9789240013131
2. RODRIGUES, F . A . R ., Da S . BOMFIM, I ., CAVALCANTI, B . C . e . al .: Eu . Chem . Bull ., 3, 2014, 358–361 .
25
DESIGN, SYNTHESIS AND BIOLOGICAL EVALUATION OF PYRAZINE-BASED
INHIBITORS OF MYCOBACTERIAL METHIONINE AMINOPEPTIDASE
JUHÁS, M ., ZITKO, J .
Depa men o Pha maceu ical Chemis y and Pha maceu ical Analysis, Facul y o Pha macy
in H adec K álo é, Cha les Uni e si y, Czech Republic
e-mail: juhasm@ a .cuni .cz
Tube culosis, caused by Mycobac e ium ube culosis (M b), is he numbe one cause o
dea hs due o a single in ec ious agen wo ldwide .
In his p ojec , we p esen he syn hesis and biological e alua ion o new po en ial
py azine-based inhibi o s (Fig . 1) o he p ominen d ug a ge mycobac e ial me hionine
aminopep idase 1 (M Me AP1) . The ac i i y o all compounds was e alua ed agains he
iso o m M Me AP1a .
O e all, high inhibi ion o he isola ed enzyme was obse ed . Howe e , as desc ibed
p e iously1, he ac i i y was s ongly dependen on he used me al co ac o . The highes
ac i i y was seen in he p esence o Ni(II) (IC50 = 0 .6 µM, 2B subs i u ion), he low-
es wi h Co(II) . Se e al compounds also showed medioc e in i o po ency agains M b
(MIC = 15 .625 µg mL−1) . Un o una ely, no di ec co ela ion wi h he ac i i y agains he
isola ed enzyme was seen . Despi e he high s uc u al simila i ies o bac e ial and ungal
Me AP o mycobac e ial M Me AP1, inal compounds did no exe any an ibac e ial no
an i ungal ac i i y .
The s udy was suppo ed by he Czech Science Founda ion (P ojec No. 20-19638Y),
and om he p ojec o Speci ic Academic Resea ch (SVV 260 547).
Re e ences
1. LU, J . P ., YE, Q . Z .: Bioo g . Med . Chem . Le ., 20, 2010, 2776–2779 .
Fig. 16
Fig. 1. Gene al s uc u e o he syn hesized compounds
32
Alkaloids a e impo an g oup o biologically ac i e seconda y me aboli es . Many o
hem inhibi human cholines e ases and he e o e ha e po en ial o be used in he ea men
o Alzheime ’s disease (AD) . Fo example, Ama yllidaceae alkaloid galan hamine is used
in he apy o AD .1
AD is one o he mos equen causes o demen ia in he wo ld . AD consis o many
cogni i e and neu opsychia ic mani es a ions . Enzymes ace ylcholines e ase (AChE) and
bu y ylcholines e ase (BuChE) play impo an ole in he p og ession o his disease .1
The genus Ficus includes a bo eous and e e g een plan s belonging o he amily
Mo aceae, ha is dis ibu ed widely h oughou he opical and sub opical egions . I
is ep esen ed by abou 725 species . Plan s om he genus Ficus con ain among o he
alkaloids . These alkaloids display a ious s uc u es and some o hem ha e in e es ing
biological ac i i ies such as an i-in lamma o y, an i umo , an i ungal, an ibac e ial and an-
imala ial .2
Wi hin he phy ochemical s udy, 19 ex ac s om lea es and s ems o 14 species o
he genus Ficus we e p epa ed . D y ma e ial was g ound and hen ex ac ed by boiling
in e hanol. E hanolic ex ac s we e pu i ied by liquid-liquid ex ac ion (e he , e hyl ac-
e a e, chlo o o m) . All ex ac s we e es ed on he abili y o inhibi human cholines e ases .
In es ing hBuChE inhibi ion po ency has been demons a ed by he ex ac AL-700C
(74 .82 ± 2 .78% a concen a ion 50 µg mL−1) .
This wo k was suppo ed by EFSA-CDN (Reg. No. CZ.02.1.01/0.0/0.0/16_019/0000841)
co- unded by ERDF and om he p ojec o Speci ic Academic Resea ch (SVV 260 548).
Re e ences
1. HULCOVÁ, D ., BREITEROVÁ, K ., SIATKA T . e al.: Molecules, 23, 2018, a . 719 .
2. KUBO, M ., YATSUZUKA, W ., MATSUSHIMA, S . e al.: Chem . Pha m . Bull ., 64, 2016, 957–960 .
NEW AMARYLLIDACEAE ALKALOIDS
FROM NARCISSUS PSEUDONARCISSUS c . CARLTON
AS INSPIRATION FOR THE DEVELOPMENT OF NEW DRUGS
FOR ALZHEIMER’S DISEASE
AL MAMUN, A .,1 CAHLÍKOVÁ, L.,1 HULCOVÁ, D .,1 MAŘÍKOVÁ, J.2
1 Depa men o Pha maceu ical Bo any, Facul y o Pha macy in H adec K álo é, Cha les Uni e si y,
Czech Republic
2 Depa men o O ganic and Bioo ganic Chemis y, Facul y o Pha macy in H adec K álo é,
Cha les Uni e si y, Czech Republic
e-mail: almamuna@ a .cuni .cz
Plan alkaloids a e one o he mos in e es ing g oups o seconda y me aboli es and a e
p esen also in he plan s o he amily Ama yllidaceae . To da e, nea ly 600 Ama yllidaceae
alkaloids (AA) ha e been isola ed .1 Na cissus pseudona cissus c . Ca l on (NPC) is an
Ama yllidaceae species, exclusi ely used o he comme cial ex ac ion o galan hamine
as a d ug o he ea men o mild o mode a e s ages o Alzheime ’s disease (AD) . The

33
ea men o AD is only symp oma ic including he apies wi h ace ylcholines e ase (AChE)
inhibi o s . Bu y ylcholines e ase (BuChE) is ano he cholines e ase (ChE), whose ac i i y
inc eases o 40–90% in he la e s age o AD b ain .1 So a , hi een known and ou no el
AA ha e been isola ed om he alkaloidal ex ac o NPC and ha e been sc eened o
AChE, BuChE, and p olyloligopep idase (POP) inhibi ion ac i i y . Th ee new compounds
named ca l onine A, B, and C demons a e signi ican inhibi ion po en ial owa ds hBuChE
(IC50 = 910 nM, 31 nM, and 14 .84 µM, espec i ely) .1 Ca l onine A also showed mode -
a e POP inhibi ion ac i i y (IC50 = 143 µM) .1 The no el compound na ciabduliine inhibi s
bo h hAChE (IC50 = 3 .29 µM) and hBuChE (IC50 = 3 .44 µM) . The nex pa o he cu en
s udy was he p epa a ion o syn he ic de i a i es s uc u ally inspi ed by ca l onines and
sc eening o hei biological ac i i ies connec ed wi h AD .
Na cissus pseudona cissus
c . Ca l on
Ca l onine A
IC50,hBuChE = 0.91 ± 0.02 μM
Ca l onine B
IC50,hBuChE = 0.031 ± 0.001μM
FC001
IC50,hBuChE = 0.240 ± 0.03μM
S uc u e de ail
Aldehyde Ty amine
+
Fig. 1. Syn hesis o s uc u al analogues o ca l onins
The p ojec was suppo ed om he p ojec o Speci ic Academic Resea ch (SVV 260 548).
Re e ences
1. AL MAMUN, A., MAŘÍKOVÁ, J., HULCOVÁ, D. e . al.: Biomolecules, 2020, 10, a . 800 .
AMARYLLIDACEAE ALKALOIDS OF NORBELLADINE-TYPE
AS INSPIRATION FOR DEVELOPMENT OF SELECTIVE
BUTYRYLCHOLINESTERASE INHIBITORS
PIDANÝ, F .,1 CAHLÍKOVÁ, L.,1 AL MAMUN, A .,1 HULCOVÁ, D .,2 MAŘÍKOVÁ, J.3
1 Depa men o Pha maceu ical Bo any, Facul y o Pha macy in H adec K álo é, Cha les Uni e si y,
Czech Republic
2 Depa men o Pha macognosy, Facul y o Pha macy in H adec K álo é, Cha les Uni e si y, Czech Republic
3 Depa men o O ganic and Bioo ganic Chemis y, Facul y o Pha macy in H adec K álo é,
Cha les Uni e si y, Czech Republic
e-mail: pidany @ a .cuni .cz
Alzheime ’s disease is a se ious and i e e sible p og essi e neu odegene a i e dis-
o de , ha will each a p e alence o mo e han 100 million by 2050 due o he aging o
34
popula ion .1 Pa hological changes in he a ec ed b ain include: in acellula neu o ib illa y
angles, ex acellula amyloid plaques, inc eased oxida i e s ess, choline gic dis unc ion,
and o he s . Choline gic neu o ansmission is e mina ed by ace ylcholine hyd olysis egu-
la ed by wo enzymes: ace ylcholines e ase (AChE) and bu y ylcholines e ase (BuChE) .
Wi h he p og ession o disease he ac i i y o AChE dec eases, while ha o BuChE
inc eases .2 The alkaloids ca l onin A and B demons a ed excep ional selec i e inhibi ion
po en ial owa ds he enzyme BuChE in ens o nanomoles (IC50 = 0 .031 ± 0 .001µM) .
Un o una ely, hese alkaloids a e p esen in plan ma e ial only in ace amoun s . The aim
o his wo k is a p epa a ion o syn he ic compounds inspi ed by alkaloids o he belladine-
ype wi h subsequen s uc u e-biological ac i i y ela ionship s udy .
The wo k was suppo ed om he p ojec o Speci ic Academic Resea ch (SVV 260 548).
Re e ences
1. KOŠAK, U ., BRUS, B ., KNEZ, D . e al.: J. Med. Chem., 61, 2018, 119‒139.
2. MEDEN, A., KNEZ, D., JUKIČ, M. e al.: Chem. Commun., 55, 2019, 3765‒3768.
PHYTOCHEMICAL INVESTIGATION
OF THE DICRANOSTIGMA FRANCHETIANUM (PRAIN) FEDDE
(PAPAVERACEAE) HERB: PRELIMINARY STUDY
WIJAYA, V .,1 KOHELOVÁ, E .,1 OPLETAL, L .,1 JENČO, J.1 ŠAFRATOVÁ, M .2
1 ADINACO Resea ch G oup, Depa men o Pha maceu ical Bo any, Facul y o Pha macy in H adec K álo é,
Cha les Uni e si y, Czech Republic
2 ADINACO Resea ch G oup, Depa men o Pha macognosy, Facul y o Pha macy in H adec K álo é,
Cha les Uni e si y, Czech Republic
e-mail: wijaya @ a .cuni .cz
Dic anos igma anche ianum (P ain) Fedde, syn . Chelidonium anche ianum
P ain (Papa e aceae) is one o he ep esen a i es o he scan y genus Dic anos igma
Hook . . & Thomson . This annual plan g ows endemically in he Himalayas and wes e n
China and is used as an o namen al plan in Eu ope . Al hough i is he sou ce o isoquino-
line alkaloids (especially isoco ydine) and he hi he o li le-s udied alkaloids (chelilu in,
cheli ubin and cheilan hi olin), he plan has no been sys ema ically s udied un il his
ime . In p ima y sc eening o he summa y alkaloid ex ac o cholines e ases inhibi ion,
he inhibi o y po ency was high (hAChE/hBChE, IC50 = 1.67 ± 0.11/3.85 ± 0.31 µg mL−1)
and oge he a leas 25 alkaloids we e ound in he ex ac . The p ima y e hanol ex ac
was p epa ed om 11 .8 kg o d y he b (Ga den o Medicinal Plan s, Facul y o Pha macy
in H adec K álo é), om which alkaloid ex ac s wi h di e en sol en s wi h inc eased
pola i y (n-hexane, die hyl e he , e hyl ace a e, chlo o o m, chlo o o m-e hanol) we e p e-
pa ed. The pu i ied die hyl e he ex ac o he alkaloidal bases (93 g) was sepa a ed by
lash ch oma og aphy on silica o gi e 12 combined ac ions. F om hese ac ions a e
pu i ica ion (+)-isoco ydine 1, p o opine 2, alloc yp opine 3, be be ine 4, chele y h ine 5,
sanguina ine 6) acco ding o he TLC compa ison ha e been ob ained so a . Thei inhibi-
35
o y ac i i y on hAChE and hBChE was de e mined by using ecombinan human b ain
cholines e ases wi h he ollowing esul s: hAChE/hBChE (IC50, mM) (1: > 1000/657.1 ±
15 .5, 2: 230.0 ± 21.0/208.9 ± 17.7, 3: 250 .0 ± 25 .2, 4: 0.71 ± 0.10/30.7 ± 3.5, 5,6: no
de e mined so a ) .
The s udy was suppo ed by he Resea ch p og am De elopmen and S udy o D ugs
(P og es Q42) and om he p ojec o Speci ic Academic Resea ch (SVV 260 548).
SEMISYNTHETIC DERIVATIVES OF AMARYLLIDACEAE ALKALOID
HAEMANTHAMINE AS POTENTIAL DRUGS IN THE TREATMENT
OF ALZHEIMER’S DISEASE
PEŘINOVÁ, R.,1 KOHELOVÁ . E .,1 ŠPULÁK, M .,2 MAŘÍKOVÁ, J.,2 HULCOVÁ, D .,1 CAHLÍKOVÁ, L.1
1 ADINACO Resea ch G oup, Depa men o Pha maceu ical Bo any, Facul y o Pha macy in H adec K álo é,
Cha les Uni e si y, Czech Republic
2 Depa men o O ganic and Bioo ganic Chemis y, Facul y o Pha macy in H adec K álo é,
Cha les Uni e si y, Czech Republic
e-mail: pe ino @ a .cuni .cz
Alzheime ’s disease (AD) is he mos p e alen neu odegene a i e disease wo ldwide
wi h complex e iology and mul i ace ed pa hophysiology and da a indica e an exponen ial
ise in he numbe o cases o his disease . The well-known Ama yllidaceae alkaloid (AA)
galan hamine is a ma ke ed d ug o AD he apy unde he comme cial name Reminyl©
(galan hamine hyd ob omide) .
S udies also poin ed ou a ious pha macological p ope ies o semisyn he ic de i a-
i es o some AA, such as alkaloid haeman hamine (HMT), which is widely dis ibu ed
h ough Ama yllidaceae plan s . Based on ou p e ious esul s, whe e se e al HMT de-
i a i es demons a ed p omising hAChe/hBuChe inhibi ion po ency, we con inued he
p epa a ion o u he HMT semisyn he ic de i a i es .1
Se e al new es e s showed in e es ing inhibi ion o bo h s udied cholines e ases, hus
s uc u e-ac i i y ela ionship (SAR) was also s udied .2 Newly p epa ed compounds we e
iden i ied by 1D-, 2D-NMR and ESI-MS me hods. The mos po en compounds we e s ud-
ied in mo e de ail (e.g., ype o inhibi ion, docking s udies, logBB e c .) .
This wo k was suppo ed om he p ojec o Speci ic Academic Resea ch (SVV 260 548).
Re e ences
1. KOHELOVÁ, E., PEŘINOVÁ, R., MAAFI, N. e al .: Molecules, 24, 2019, a . 1307 .
2. PEŘINOVÁ, R., MAAFI, N., KORÁBEČNÝ, J. e al .: Bioo g . Chem ., 100, 2020, a . 103928 .
36
IN VITRO ANTIAGGREGATION POTENTIAL OF SELECTED ISOQUINOLINE
ALKALOIDS
PARVIN, M . S .,1 KARLÍČKOVÁ, J.,2 HRUBŠA, M .,3 FADRAERSADA, J .,3 MLADĚNKA, P.,3
MACÁKOVÁ, K .1
1 Depa men o Pha macognosy, Facul y o Pha macy in H adec K álo é, Cha les Uni e si y, Czech Republic
2 Depa men o Pha maceu ical Bo any, Facul y o Pha macy in H adec K álo é, Cha les Uni e si y,
Czech Republic
3 Depa men o Pha macology and Toxicology, Facul y o Pha macy in H adec K álo é, Cha les Uni e si y,
Czech Republic
e-mail: pa ins@ a .cuni .cz
The pla ele is an anuclea e cell ci cula ing in he bloods eam . The no mal pla e-
le unc ion is o egula e haemos asis bu in a pa hological s a e, such as endo helial
dys unc ion, enhanced pla ele agg ega ion can lead o ce ain ca dio ascula diseases
such as s oke, acu e myoca dial in a c ion e c .1 Some plan seconda y me aboli es, al-
kaloids in pa icula , a e p omising candida es in he de elopmen o an ipla ele d ugs .2
So a , ou een isoquinoline alkaloids ha e been sc eened o inhibi ion o pla ele ag-
g ega ion induced by a achidonic acid and collagen and compa ed wi h he s anda d d ug
ace ylsalicylic acid . The sc eening was pe o med by impedance agg egome y using
whole human blood . Papa e ine and bulbocapnine demons a ed inhibi ion a he con-
cen a ion o 80 µM. Thei mechanisms o ac ion could be an in luence on a achidonic
acid cascade including cyclooxygenase-1, h omboxane A2 syn hase, and an agonism a
h omboxane A2 ecep o s . The an iagg ega ion ac i i y o papa e ine and bulbocapnine
seems o be ela ed o an agonism a h omboxane ecep o s . In addi ion o an ipla ele
ac i i y, he p o h ombin ime and ac i a ed pa ial h omboplas in ime o all alkaloids
ha e been de e mined and none o he alkaloids showed an icoagulan e ec s in human
plasma .
The s udy was suppo ed om he p ojec o Speci ic Academic Resea ch (SVV 260 548).
Re e ences
1. KARLÍČKOVÁ, J., ŘÍHA, M., FILIPSKÝ, T. e al.: Plan a . Med ., 82, 2016, 76–83 .
2. QURRAT-UL-AIN, KHAN, H ., MUBARAK, M . S . e al.: F on . Pha macol ., 7, 2016, a . 292 .
SEMI-SYNTHETIC DERIVATIVES OF AMARYLLIDACEAE ALKALOID
AMBELLINE AND THEIR CYTOTOXIC POTENTIAL
RITOMSKÁ, A .,1 PEŘINOVÁ, R.,1 MAŘÍKOVÁ, J.,2 HAVELEK, R .,3 CAHLÍKOVÁ, L.1
1 ADINACO Resea ch G oup, Depa men o Pha maceu ical Bo any, Facul y o Pha macy in H adec K álo é,
Cha les Uni e si y, Czech Republic
2 Depa men o O ganic and Bioo ganic Chemis y, Facul y o Pha macy in H adec K álo é,
Cha les Uni e si y, Czech Republic
3 Depa men o Biochemis y, Facul y o Medicine in H adec K álo é, Cha les Uni e si y, Czech Republic
e-mail: i omska@ a .cuni .cz
37
Ama yllidaceae alkaloid ambelline, belonging o he c inane- ype g oup, lacks any
signi ican biological ac i i y. Howe e , i s analogues p epa ed by he de i a iza ion o
C11-hyd oxyl g oup possess a ious in e es ing p ope ies (e.g ., inhibi o y ac i i y o cho-
lines e ases, an imala ial ac i i y) . As a con inua ion o ou ea lie wo k and ex ension
o he p epa ed de i a i es scale, ele en no el a oma ic es e s we e de eloped (LC-108,
LC-180, LC-181, LC-177, LC-131, LC-189, LC-179, LC-119, LC-110, LC-106, LC-
178) . To cha ac e ize hei biological ac i i y spec um, MTT assays we e pe o med o
de e mine hei cy o oxic po en ial . To p edic he s uc u e-ac i i y ela ionship o u he
esea ch, subs ances desc ibed in ou p e ious wo k we e also included in his cy o oxic-
i y s udy .1 Molecules wi h he mos p onounced cy o oxic ac i i y con ain a me hyl g oup
(LC-108), me hoxy g oup (LC-180, LC-176, LC-104, LC-181), e hoxy g oup (LC-182),
o disubs i u ion wi h di e en unc ional g oups (LC-106) on C11 .
The s udy was suppo ed om he p ojec o Speci ic Academic Resea ch (SVV 260 548).
Re e ences
1. MAŘÍKOVÁ, J., RITOMSKÁ, A., KORÁBEČNÝ, J . e al .: J . Na . P od ., 83, 2020, 1359–1367 .
INDOLE ALKALOIDS FROM VINCA MINOR L . AND THEIR BIOLOGICAL
ACTIVITY
VRABEC, R .,1 HULCOVÁ, D .,1 MAŘÍKOVÁ, J.,2 KUNEŠ, J .,2 HAVELEK, R .,3 LOČÁREK, M.,4
JENČO, J.,4 ŠAFRATOVÁ, M .,1 OPLETAL, L .4
1 ADINACO Resea ch G oup, Depa men o Pha macognosy, Facul y o Pha macy in H adec K álo é,
Cha les Uni e si y, Czech Republic
2 Depa men o O ganic and Bioo ganic Chemis y, Facul y o Pha macy in H adec K álo é,
Cha les Uni e si y, Czech Republic
3 Depa men o Medical Biochemis y, Facul y o Medicine in H adec K álo é, Cha les Uni e si y,
Czech Republic
4 ADINACO Resea ch G oup, Depa men o Pha maceu ical Bo any, Facul y o Pha macy in H adec K álo é,
Cha les Uni e si y, Czech Republic
e-mail: abec @ a .cuni .cz
Vinca mino L . (Apocynaceae), an e e g een ailing subsh ub common in Wes e n
and Sou he n Eu ope, is a ich mono e pene indole alkaloid sou ce . So a , we ha e iso-
la ed 23 alkaloids om ae ial pa s o V. mino , 12 o hem we e epo ed in his species
o he i s ime. Two alkaloid s uc u es a e en i ely new. The names cosimonine and
incamino udeine a e p oposed, and ela i e con igu a ion de e mined. In an ongoing
s udy in o he disco e y o new an i-neu odegene a i e d ugs om na u al sou ces, we
ha e es ed ou isola ed compounds o inhibi human ace ylcholines e ase (hAChE) and
bu y ylcholines e ase (hBuChE) . None o he alkaloids we e ac i e agains hAChE, how-
e e , mos s uc u es showed in e es ing inhibi ion o hBuChE wi h IC50 < 100 µM . In he
la e and se e e s age o Alzheime ’s disease (AD), he exp ession o AChE is educed,
bu he exp ession BuChE is inc eased and akes o e i s ole . BuChE is also in ol ed
in o he pa hological AD p ocesses, such as he p oduc ion o neu o ib illa y angles

38
and he o ma ion o β-amyloid plaques. The ac i e subs ances we e also e alua ed o
he p obabili y o a blood-b ain ba ie pene a ion (logBB) by in silico compu a ional
me hod . The cy o oxici y o isola ed compounds was assessed on he panel o 10 umo -
ous cell lines. Excep o ebu namonine, none o he es ed alkaloids showed signi ican
cy o oxic ac i i y .
The s udy was suppo ed by he Resea ch p og am De elopmen and S udy o D ugs
(P og es Q42) and om he p ojec o Speci ic Academic Resea ch (SVV 260 548).
AROMATIC DERIVATIVES OF HAEMANTHAMINE-TYPE ALKALOID
VITTATINE AS POTENTIAL LIGANDS FOR ALZHEIMER’S DISEASE
AL SHAMMARI, L .,1 HULCOVÁ, D .,1,2 OPLETAL, L .,1 CAHLÍKOVÁ, L.1
1 ADINACO Resea ch G oup, Depa men o Pha maceu ical Bo any, Facul y o Pha macy in H adec K álo é,
Cha les Uni e si y, Czech Republic
2 Depa men o Pha macognosy, Facul y o Pha macy in H adec K álo é, Cha les Uni e si y, Czech Republic
e-mail: alshamml@ a .cuni .cz
Recen esea ch on Ama yllidaceae plan amily epo s he isola ion o mo e han 600
di e en Ama yllidaceae alkaloids (AA) wi h di e en s uc u e ypes possessing wide
ange o biological ac i i ies . Among he mos impo an biological ac i i ies o AA belong
ac i i ies associa ed wi h Alzheime ’s disease (AD) . Alzheime ’s disease (AD) is he mos
p e alen neu odegene a i e disease wo ldwide wi h complex e iology and mul i ace ed
pa hophysiology and da a indica e an exponen ial ise in he numbe o cases o his dis-
ease . Galan hamine is he one o he mos impo an AA used o ea men o AD and
comme cially a ailable unde he name Reminyl® (galan hamine hyd ob omide) .
Based on ou p e ious published wo k o Hippeas um x hyb idum c . Fe a i 18 di e -
en alkaloids ha e been isola ed so a and hey we e iden i ied by MS, HRMS and 1D- and
2D-NMR echniques . All alkaloids we e es ed o hei ac i i ies associa ed wi h AD
(hAChE, hBuChE and POP) and hei abili y o inhibi he g ow h o se e al cance cell
lines . Mo eo e , he isola ed amoun and he s uc u e o i a ine allowed us o de elop
and syn hesize hi een new a oma ic es e s o he haeman hamine- ype alkaloid i a ine .
All he semisyn he ic de i a i es we e s udied o hei inhibi o y po en ial agains bo h
hAChE and hBuChE . The po en ial candida es we e selec ed o measu e he abili y o
pene a e he blood-b ain ba ie (BB) and a ailabili y o he CNS .
The s udy was suppo ed om he p ojec o Speci ic Academic Resea ch (SVV 260 548).
Re e ences
1. AL SHAMMARI, L., HULCOVÁ, D., MAŘÍKOVÁ, J. e al .: S . A . J . Bo ., 136, 2021, 137–146 .
39
SEPARATION OF THE CAROTENOID MYXOXANTHOPHYLL
FROM SYNECHOCYSTIS SALINA BY HIGH PERFORMANCE
COUNTERCURRENT CHROMATOGRAPHY AND EVALUATION
OF ITS IMMUNE-STIMULATING PROPERTIES
FÁBRYOVÁ, T .,1,2 NOVÁKOVÁ, M .,1,2 VOKURKOVÁ, D .,3 KOPECKÝ, J .,2 HROUZEK P .,2 CHEEL, J .,2
TŮMOVÁ, L.1
1 Depa men o Pha macognosy, Facul y o Pha macy in H adec K álo é, Cha les Uni e si y, Czech Republic
2 Labo a o y o Algal Bio echnology, The Cen e ALGATECH, Ins i u e o Mic obiology,
The Czech Academy o Sciences, Czech Republic
3 Ins i u e o Clinical Immunology and Alle gology, Facul y o Medicine in H adec K álo é,
Cha les Uni e s i y and Uni e si y Hospi al H adec K álo é, Czech Republic
e-mail: ab yo @ a .cuni .cz
Cyanobac e ium Synechocys is salina is well-known o biosyn hesizing di e en ypes
o pigmen s including chlo ophyll, ca o enoids and phycobilip o eins, many o which ha e
a ac ed he a en ion o he indus ies and esea che s due o hei a ied bio- unc ionali y
and applica ions . One o i s syn hesized ca o enoid pigmen s is myxoxan hophyll (Fig . 1),
a glycosyla ed monocyclic ca o enoid ha is a ely ound in na u e . This yellow pigmen
has been shown o exhibi an ioxidan and an i-hype glycemic ac i i ies .1,2 Mo eo e , i s
po en ial in he p ophylac ic and/o he apeu ic ea men o undesi able condi ions due o
oxida i e p ocesses has also been disclosed .3 To he bes o ou knowledge, his pigmen
has no ye been o e ed comme cially, and i s bio- unc ional p ope ies o in e es in he
ood, nu aceu ical and cosme ic sec o s ha e no been ex ensi ely s udied . In his s udy,
myxoxan hophyll was isola ed om Synechocys is salina by high pe o mance coun e -
cu en ch oma og aphy (HPCCC) and i s iden i y was con i med using high-pe o mance
liquid ch oma og aphy connec ed o a high- esolu ion andem mass spec ome y de ec-
o wi h elec osp ay ioniza ion sou ce (HPLC-ESI-HRMS/MS). In addi ion, he po en ial
ac i a ion e ec on immune cells in esponse o myxoxan hophyll ea men was in es i-
ga ed, measu ing cell su ace CD69 exp ession using low cy ome y. An inc ease in he
numbe o g anulocy es was obse ed a e myxoxan hophyll ea men . The p esen ed
da a may suppo he po en ial use o myxoxan hophyll o s eng hening he immune
sys em agains bac e ial and ungal in ec ions .
Fig. 19
Fig. 1. Chemical s uc u e o myxoxan hophyll
40
The s udy was suppo ed by Na ional Sus ainabili y P og amme I o he Minis y o
Educa ion, You h and Spo s o he Czech Republic (P ojec No. LO1416) and om he
p ojec o Speci ic Academic Resea ch (SVV 260 548).
Re e ences
1. GHOSH, T ., BHAYANI, K ., PALIWAL, C . e al.: F on . Ma . Sci ., 3, 2016, a . 146 .
2. STEIGER, S ., SCHÄFER, L ., SANDMANN, G .: J . Pho ochem . Pho obiol . B: Biol ., 52, 1999, 14–18 .
3. JAEGER, C ., SAETTLER, A ., SCHROEDER, K . R . e al.: WO2002024183A1, 28 . 03 . 2002 .
DERIVATIVES OF MONTANINE-TYPE ALKALOIDS AND THEIR IMPLICATION
TO ALZHEIMER’S DISEASE: SYNTHESIS, BIOLOGICAL ACTIVITY,
DOCKING STUDY
MAAFI, N .,1 CAHLÍKOVÁ, L.,1 MAŘÍKOVÁ, J.,2 HULCOVÁ, D .3
1 ADINACO Resea ch G oup, Depa men o Pha maceu ical Bo any, Facul y o Pha macy in H adec K álo é,
Cha les Uni e si y, Czech Republic
2 Depa men o O ganic and Bioo ganic Chemis y, Facul y o Pha macy in H adec K álo é,
Cha les Uni e si y, Czech Republic
3 ADINACO Resea ch G oup, Depa men o Pha macognosy, Facul y o Pha macy in H adec K álo é,
Cha les Uni e si y, Czech Republic
e-mail: nega m@ a .cuni .cz
The Ama yllidaceae plan amily is one o he mos impo an alkaloid con aining
plan amilies wi h biological p ope ies such as an i umo , an imic obial, an imala ial,
and signi ican an ineu odegene a i e ac i i ies. Among all Ama yllidaceae alkaloids,
mon anine- ype alkaloids a e cha ac e ized by 5,11-me hanomo phan h idine ing sys em
and known o hei po en ial an ip oli e a i e, an ibac e ial, an imala ial, an i heuma ic
and an icholines e ase ac i i ies .1 The e ec o mon anine as an inhibi o o ace ylcho-
lines e ase has been epo ed in a dose-dependen pa e n wi h mo e han 50% inhibi ion
o enzyme a 1 mM concen a ion, in oducing mon anine as a mode a e inhibi o o ace-
ylcholines e ase .2
In his s udy, wen y-eigh new de i a i es o mon anine- ype alkaloids we e syn he-
sized and e alua ed o hei abili y o inhibi human ecombinan ace ylcholines e ase
(hAChE) and bu y ylcholines e ase (hBuChE) . Among all, 3 de i a i es o 3-O-me hyl-
panc acine showed signi ican selec i e inhibi o y po ency o hAChE (IC50 alues o 1 .6 ±
0 .1 µM, 3 .1 ± 0 .2 µM, and 4 .3 ± 0 .5 µM) . De i a iza ion o 3-O-me hylpanc acine using
1-pipe idineca bonyl chlo ide esul ed o he mos po en hBuChE inhibi o wi h IC50 o
1 .73 ± 0 .05 µM . The same acyl changes on C4 o mon anine led o educ ion o inhibi o y
ac i i y on bo h enzymes .
The s udy was suppo ed om he p ojec o Speci ic Academic Resea ch (SVV 260 548).
Re e ences
1. KOUTOVÁ, D ., MAAFI, N ., HAVELEK, R . e al .: Molecules, 25, 2020, a . 2337 .
2. PAGLIOSA, L . B ., MONTEIRO, S . C ., SILVA, K . B . e al .: Phy omedicine, 17, 2010, 698–701 .
41
PHARMACEUTICAL TECHNOLOGY SECTION
THE ROLE OF pH IN THE FORMATION OF SKIN LIPID BARRIER
SAGRAFENA, I .,1 NOVÁČKOVÁ, A.,1 PARASKEVOPOULOS, G .,1 PULLMANNOVÁ, P .,2
DWIVEDI, A .,2 MAZUMDER, A .,2 VÁVROVÁ, K .2
1 Depa men o Pha maceu ical Technology, Facul y o Pha macy in H adec K álo é, Cha les Uni e si y,
Czech Republic
2 Depa men o O ganic and Bioo ganic Chemis y, Facul y o Pha macy in H adec K álo é,
Cha les Uni e si y, Czech Republic
sag a ei@ a .cuni .cz
The skin’s pH has he peculia cha ac e is ic o being nea -neu al (pH ~ 7 .4) in deepe
laye s o he epide mis, while i becomes acidic (pH ~ 5 .5) on he su ace o he s a um
co neum (SC) .1 As i has been p e iously sugges ed, he skin’s “acid man le” con ib-
u es o he p o ec ion agains pa hogens, he ac i a ion o enzymes o skin unc ion,
he inhibi ion o enzymes pe u bing SC in eg i y, and inally, he impedance o he p o-
in lamma o y cy okines elease.2 This s udy sugges s a new ole o he skin’s pH, closely
ela ed o he o ma ion o he unique mul ilamella s uc u e o he lipidic ma ix in he
SC which is essen ial o he excellen skin ba ie unc ion . Isola ed human SC lipids
model memb anes we e ea ed wi h bu e pH 5 .5 o pH 7 .4 . X- ay di ac ion showed
ha acidic pH ea ed lipids o med long pe iodici y phase (d = 13 .53–13 .72 nm), sho
pe iodici y phase (d = 5 .56–5 .60 nm), aces o choles e ol phase and o la e al packing
o ho hombic con o ma ion ( wo e lec ions a 4.1 and 3.7 nm). On he o he hand, pH
7 .4 ea ed lipids showed poo ly esol ed di ac og ams wi h aces o long pe iodici y
phase and a p e alen unknown peak a q = 1 .35 nm−1 . The unc ional consequence o
he pH-d i en change in lipid mic os uc u e was an inc eased ansepide mal wa e loss
a pH 7 .4 (27 ± 5 .0 g m−2 h) compa ed o pH 5 .5 (21 ± 5 .2 g m−2 h) in ei he model lipid
memb anes o isola ed SC . These esul s a e consis en wi h he diminished ba ie unc-
ion in newbo n babies, elde ly o pa ien s wi h a opic de ma i is, whe e SC acidi ica ion
is incomple e .
The s udy was suppo ed by he Czech Science Founda ion (P ojec No. 19-09135J),
by he G an Agency o Cha les Uni e si y (P ojec No. 1156120) and om he p ojec o
Speci ic Academic Resea ch (SVV 260 547).
Re e ences
1. ELIAS, P . M .: Exp . De ma ol . 26, 2017, 999–1003 .
2. PROKSCH, E .: J . De ma ol ., 45, 2018, 1044–1052 .
48
skin ba ie lipids . Ou p elimina y da a ha e shown ha he e is a di ec dependence
o monolaye o ma ion on he numbe o e minal amino g oups o each dend ime .
Mo e speci ically, di e en gene a ions (G2, G3 and G4) o PAMAM dend ime s we e
s udied in di e en concen a ions . In e es ingly, when G4 PAMAM dend ime was used
in di e en concen a ions (2.5, 5 o 10 μM), he o ganiza ion o lipids o monolaye
was a ec ed mos by he lowes dend ime concen a ion . Addi ional expe imen s a e in
p og ess o e alua e he le el o in e ac ion be ween he di e en PAMAM gene a ions
and he skin ba ie lipids .
The s udy was suppo ed by he Czech Science Founda ion (P ojec No. 19-09600S)
and om he p ojec o Speci ic Academic Resea ch (SVV 260 547).
Re e ences
1. SUN, M ., FAN, A ., WANG, Z . e al.: So Ma e , 8, 2012, 4301–4305 .
2. DAVE, K ., VENUGANTI, V .: The . Deli ., 8, 2017, 1077–1096 .
EFFECT OF POLYMER COMBINATIONS ON THE DISSOLUTION PROFILES
OF A MODEL DRUG IN BIORELEVANT MEDIA
OGADAH, C., VRANÍKOVÁ, B., MARUSHKA, J., ŠKLUBALOVÁ, Z.
Depa men o Pha maceu ical Technology, Facul y o Pha macy in H adec K álo é, Cha les Uni e si y,
Czech Republic
e-mail: ogadahc@ a .cuni .cz
Con olled elease d ug deli e y sys ems a e used o op imizing he apeu ic e icacy,
wi h he iew o maximizing bioa ailabili y and educing side e ec s . The mos widely
used s a egy o con olling he elease o d ugs in ol es he use o hyd ophilic swella-
ble polyme s as he elease- e a dan ma e ial, in he o m o ma ix sys ems . In his
wo k, he e ec o combining wo polyme s o he pu pose o ailo ing he d ug elease
cha ac e is ics o ma ix sys ems was s udied . Theophylline-loaded ma ix able s using
gua gum, hyd oxyp opyl me hylcellulose (HPMC) and hei combina ions in di e en
a ios wi hou any addi ional excipien s (e.g., ille s, lub ican s) we e p epa ed by di ec
comp ession . Dissolu ion s udies we e pe o med o 24 hou s in h ee bio ele an me-
dia – Fas ed s a e Simula ed Gas ic, In es inal and Colon Fluids (FaSSGF, FaSSIF and
FaSSCoF) o pH 1 .6, 6 .5 and 7 .8, espec i ely . The esul s indica ed desi ed sus ained
elease p o iles o all o mula ions wi h a ia ion in d ug elease wi h espec o he
p opo ion o each polyme . Mo eo e , i was obse ed ha he pH-independen elease
may be achie ed by combining he polyme s . These o mula ions which a e essen ially
pH-independen could lead o a mo e p edic able dissolu ion p o ile, which is desi able
in he ea men o ailmen s whe e he e is a cons an luc ua ion in he GIT pH (e.g.,
in lamma o y bowel diseases). I is expec ed ha a ying he a ios o used polyme s
would op imize he mucoadhesion po en ial as well . This aspec will be explo ed in
u u e s udies .

49
The s udy was suppo ed by he G an Agency o Cha les Uni e si y (P ojec
No. 70119/2019) and om he p ojec o Speci ic Academic Resea ch (SVV 260 547).
SELF-EMULSIFYING DRUG DELIVERY SYSTEMS ENABLE ORAL
OLIGONUCLEOTIDE DELIVERY
KUBAČKOVÁ, J.,1 HOLAS, O .,1 ZBYTOVSKÁ, J .,1 PÁVEK, P .,2 MULLERTZ, A .3
1 Depa men o Pha maceu ical Technology, Facul y o Pha macy in H adec K álo é, Cha les Uni e si y,
Czech Republic
2 Depa men o Pha macology and Toxicology, Facul y o Pha macy in H adec K álo é, Cha les Uni e si y,
Czech Republic
3 Depa men o Pha macy, Uni e si y o Copenhagen, Copenhagen, Denma k
e-mail: kubackja@ a .cuni .cz
Oligonucleo ide-based d ugs ep esen a highly speci ic he apeu ic app oach. How-
e e , o al deli e y o hese d ugs is hampe ed by hei low s abili y and poo pe meabili y .
The e o e, we o mula e an oligonucleo ide (OND) in o a well-es ablished o al sel -emul-
si ying d ug deli e y sys em (SEDDS) .1 Hyd ophilic OND was e ec i ely complexed
by hyd ophobic ion pa ing wi h a ca ionic lipid, ei he dime hyldioc adecylammonium
b omide (DDAB) o 1,2-dioleoyl-3- ime hylammonium-p opane (DOTAP) .2 Resul ing
hyd ophobic complexes enabled loading in o a lipid-based SEDDS con aining in es inal
pe mea ion enhance s . Nega i ely cha ged Ci em SEDDS and neu al S anda d SEDDS
we e es ed in e ms o OND p o ec ion agains nucleases and pe meabili y in i o ac oss
in es inal Caco-2 cell monolaye . Nega i e su ace cha ge o Ci em SEDDS was ound o
in e e e wi h OND complexes and hus diminished i s p o ec i e e ec agains nuclease
o 16% . Simul aneously, nega i e cha ge hinde s in e ac ions wi h nega i e cell su ace
esul ing in low pe mea ion . Wi hou nega i e su ace cha ge, neu al S anda d SEDDS
p o ec ed 58% o OND . Due o enhanced in e ac ions wi h cells, he pe mea ion o OND
in S anda d SEDDS mo e han doubled . An app op ia e in i o model could shed mo e
ligh on pe o mance o hese p omising no el o mula ions .
The s udy was suppo ed by EFSA-CDN (Reg. No. CZ.02.1.01/0.0/0.0/16_019/0000841)
co- unded by ERDF and om he p ojec o Speci ic Academic Resea ch (SVV 260 547).
Re e ences
1 . MULLERTZ, A ., OGBONNA, A ., REN, S . e al.: J . Pha m . Pha macol ., 62, 2010, 1622–1636 .
2. HAUPTSTEIN, S ., PRUFERT, F ., BERNKOP-SCHNURCH, A .: In . J . Pha m ., 487, 2015, 25–31 .
50
SURFACE ENERGY ANALYSIS OF BINARY MELOXICAM
POWDER MIXTURES USING INVERSE
GAS CHROMATOGRAPHY
BROKEŠOVÁ, J .,1 KOKTAN, J .,2 KUENTZ, M .,3 ŠKLUBALOVÁ, Z .1
1 Depa men o Pha maceu ical Technology, Facul y o Pha macy in H adec K álo é, Cha les Uni e si y,
Czech Republic
2 Depa men o Resea ch and De elopmen , Zen i a, k . s ., P ague, Czech Republic
3 Ins i u o Pha ma Technology, School o Li e Sciences in Mu enz, Uni e si y o Applied Sciences and A s
No hwes e n Swi ze land, Swi ze land
e-mail: b okesoj@ a .cuni .cz
Nowadays, imp o ing a dissolu ion a e o poo ly wa e -soluble d ugs is one o he
majo challenges o pha maceu ical esea ch . The aim o his wo k was o analyze su ace
ene gy based on in e se gas ch oma og aphy o de e mine su ace p ope ies as a p econdi-
ion o in e ac i e powde mix u es o ma ion .
The in e ac i e powde mix u es o meloxicam (MX, BCS class II) and chi osan (CH)
we e p epa ed in di e en a ios using physical mixing and co-milling . The dispe si e
and speci ic componen s o he su ace ene gy we e de e mined using non-pola (hexane,
hep ane, oc ane, nonane) and pola (dichlo ome hane, e hyl ace a e, chlo o o m, oluene,
e hanol, ace one, 1,4-dioxane) p obes, espec i ely . The ac ional sample su ace co e age
(5%) was cons an and ca ie gas (helium) wi h he low a e o 10 mL min−1 was used .
The esul s showed he highe dispe si e γD = 46 .5 mJ m−2 and lowe speci ic γSP =
2 .9 mJ m−2 componen o MX ha ing an acidic na u e, while a lowe dispe si e γD =
40 .5 mJ m−2 and highe speci ic γSP = 4 .5 mJ m−2 componen was de ec ed o CH wi h
a basic na u e .
The cohesion o ces o he d ug pa icles we e in balance wi h d ug-ca ie adhesion
o ces (exp essed as he wadh/wcoh a io ha was close o one) indica ing he success ul
p oduc ion o an in e ac i e mix u e and i s s abili y . The o al su ace ene gy was ound
o inc ease a e milling bu a massi e su ace amo phiza ion o d ug was no obse ed,
which is bene icial o d ug s abili y.
The s udy was suppo ed by he G an Agency o Cha les Uni e si y (P ojec
No. 268120/2020), by he Pha maceu ical Applied Resea ch Cen e (The PARC), Zen i a,
k. s. and om he p ojec o Speci ic Academic Resea ch (SVV 260 547).
MICROEMULSIONS FOR DERMAL DELIVERY OF IMIQUIMOD
PANOUTSOPOULOU, E .,1 PARASKEVOPOULOS, G .,1 VÁVROVÁ, K .,2 ZBYTOVSKÁ, J .1
1 Depa men o Pha maceu ical Technology, Facul y o Pha macy in H adec K álo é, Cha les Uni e si y,
Czech Republic
2 Depa men o O ganic and Bioo ganic Chemis y, Facul y o Pha macy in H adec K álo é,
Cha les Uni e si y, Czech Republic
e-mail: panou se@ a .cuni .cz
51
Imiquimod (IMQ) is a opically-applied imidazoquinoline used o he ea men o
se e al skin diseases, like ac inic ke a osis and basal cell ca cinoma .1 T adi ional o mula-
ions es ic IMQ’s e iciency o de mal deli e y because o he d ug’s poo solubili y and
low cu aneous pe meabili y .1 The aim o his wo k was he de elopmen and e alua ion
o an IMQ con aining, skin- iendly mic oemulsion sys em in en ed o opical deli e y .
A pseudo- e na y phase diag am was cons uc ed using a mix u e o phospholipids in
e hanol as a su ac an sys em and oleic acid as he oil phase . The physicochemical p op-
e ies o selec ed o mula ions we e de e mined in e ms o pa icle size, conduc i i y, and
heology . The IMQ skin up ake was e alua ed by ex i o pe mea ion expe imen in ull-
hickness human skin . Two o he p epa ed o mula ions we e able o deli e he ac i e
subs ance mo e e icien ly han he comme cial o mula ion. In addi ion, he ba ie unc-
ion o mic oemulsion ea ed skin eco e ed as e han ha o he con ol, as was shown
om ansepide mal wa e loss expe imen s . In a ed spec oscopy showed he possible
pene a ion o he mic oemulsion componen s in o he skin a a molecula le el . In conclu-
sion, he p esen ed indings demons a e ha phospholipid mic oemulsions could become
a p omising al e na i e in he opical adminis a ion o IMQ .
The s udy was suppo ed by he Czech Science Founda ion (P ojec No. 19-09600S)
and om he p ojec o Speci ic Academic Resea ch (SVV 260 547).
Re e ences
1 . MA, M ., WANG, J ., GUO, F . e al .: J . Ma e . Sci .: Ma e . Med ., 26, 2015, a . 192 .
PHARMACEUTICAL ANALYSIS AND BIOANALYTICAL CHEMISTRY
SECTION
OPEN DATABASE SEARCH FOR ILLUMINATING THE “DARK MATTER”
OF BOTTOM-UP PROTEOMICS
LENČO, J.
Depa men o Analy ical Chemis y, Facul y o Pha macy in H adec K álo é, Cha les Uni e si y,
Czech Republic
e-mail: lenco@ a .cuni .cz
Despi e he ad ancemen s in p o eomic ins umen a ion, a signi ican po ion o MS/
MS spec a om bo om-up analyses s ill e ade iden i ica ion, e en hough he spec a
quali y is su icien . This “da k ma e ” o p o eomics usually comp omises biologically
ele an componen s such as uncommon and a e pos ansla ional modi ica ions, p o-
ein sequence polymo phisms, e c .1 A la ge ac ion o unassigned MS/MS spec a is also
a consequence o unexpec ed p o ein clea age si es o pep ide modi ica ions du ing sample
handling .
We ha e ecen ly sc u inized he ad e se e ec s o he combina ion o ele a ed col-
umn empe a u e, ex ended in-column esidence ime, and low pH o he mobile phase
52
on yp ic pep ides in eg i y du ing LC-MS p o eomic analyses . To desc ibe possible pep-
ide modi ica ions in an unbiased ashion, we ook ad an age o an open da abase sea ch
o MS/MS spec a ollowed by mul i a ia e s a is ical analysis. In his way, we e ealed
ha pep ides bound o he s a iona y phase can unde go a ious a i icial modi ica ions.
Mo eo e , we se endipically disco e ed ha pep ides can be a i icially o myla ed be o e
LC-MS analyses due o dissol ing hem in a solu ion con aining a me e 0 .1% o mic acid .
We u ilized he gained expe ience in he open-da abase sea ch o cla i y wha changes o
a model p o ein induces an i adia ed ph halocyanine o pho odynamic he apy .
This s udy was suppo ed by he STARSS p ojec (Reg. No. CZ.02.1.01/0.0/0.0/15_003/
0000465) co- unded by ERDF and om he p ojec o Speci ic Academic Resea ch (SVV
260 548).
Re e ences
1. SKINNER, O . S ., KELLEHER, N . L .: Na . Bio echnol ., 33, 2015, 717–718 .
PERSPECTIVES OF USE OF PROPIONIC ACID TO INCREASE
THE SENSITIVITY OF PROTEOMIC BOTTOM-UP LC-MS METHODS
NAPLEKOV, D., JADEJA, S., LENČO, J., SKLENÁŘOVÁ, H.
Depa men o Analy ical Chemis y, Facul y o Pha macy in H adec K álo é, Cha les Uni e si y,
Czech Republic
e-mail: naplekod@ a .cuni .cz
P o eomic LC-MS analyses can iden i y and quan i y p o eins and pep ides and cha -
ac e ize hei modi ica ions, in e ac ions be ween p o einous and o he molecules, e c .1
P o eomic samples a e usually o limi ed quan i y, and hey consis o an eno mous numbe
o analy es p esen in small concen a ions below he le el o app op ia e MS de ec ion
by ypical analy ical low LC-ESI-MS. Al hough nanocolumns wi h an inne diame e o
0 .075 mm ha e been success ully implemen ed o p o eomics o in oduce pep ides ia
nano-elec osp ay ioniza ion o a mass spec ome e wi h he igh in ensi y, hey s ill ail
o p o ide su icien sensi i i y o he mos demanding analyses, such as in single-cell
p o eomics . Cu en ly, se e al s a egies a e conside ed o inc ease sensi i i y in p o eomic
LC-MS analyses. The modi ica ion o he mobile phase composi ion ep esen s he mos
s aigh o wa d one .
We ha e ecen ly demons a ed ha eplacing 0 .1% o mic acid in he mobile phase
by 1% p opionic acid signi ican ly inc eased peak in ensi ies o i e s anda d pep ides.
Thus, we us ha eplacing 0 .1% o mic acid in he mobile phase wi h an op imized
concen a ion o weake p opionic acid will inc ease he MS sensi i i y in eal-li e LC-MS
p o eomic analyses .
This s udy was suppo ed by he STARSS p ojec (Reg. No. CZ.02.1.01/0.0/0.0/15_003/
0000465) co- unded by ERDF and om he p ojec o Speci ic Academic Resea ch (SVV
260 548).
53
Re e ences
1. GUPTA, N ., TANNER, S ., JAITLY, N . e al.: Genome Res., 17, 2007, 1362‒1377.
EVALUATING THE EFFECT OF LOWER FORMIC ACID CONCENTRATION
IN MOBILE PHASE FOR PROTEMIC LC-MS ANALYSIS
JADEJA, S., LENČO, J., SKLENÁŘOVÁ, H.
Depa men o Analy ical Chemis y, Facul y o Pha macy in H adec K álo é, Cha les Uni e si y,
Czech Republic
e-mail: jadejas@ a .cuni .cz
Ideal peak shapes o pep ides in p o eomic LC-MS analyses ha e been adi ionally ob-
ained when using mobile phases o high ionic s eng h, bu in u n, supp ess elec osp ay
ioniza ion . Recen ad ancemen s in he s a iona y phases ha e in oduced he Cha ged Su -
ace Hyb id (CSH) echnology .1 Re e sed s a iona y phase wi h CSH echnology p oduces
peak shapes wi h a mobile phase o lowe ionic s eng h equi alen o hose when a highe
ionic s eng h mobile phase is used .
Unde he scope o he s udy, we will e alua e he e ec o educed o mic acid con-
cen a ion in he mobile phase on peak symme y, MS sensi i i y, he ex en o pep ide
iden i ica ion, and he a e o a i icial modi ica ion. The da a on peak cha ac e is ics ob-
ained om he ad anced CSH column a he a ied o mic acid concen a ion (0 .1% o
0 .01%) we e compa ed wi h an equi alen e e sed-phase column, which is widely used o
analyze p o eomic samples . A well-cha ac e ized se o pep ides wi h a ied p ope ies and
cha ge s a es we e included . Because o he su ace cha ged p ope y o he CSH column,
much imp o ed peak shapes we e ob ained a a lowe concen a ion o o mic acid when
compa ed o he equi alen e e sed-phase column .
This s udy was suppo ed by he STARSS p ojec (Reg. No. CZ.02.1.01/0.0/0.0/15_003
/0000465) co- unded by ERDF and om he p ojec o Speci ic Academic Resea ch (SVV
260 548).
Re e ences
1. LAUBER, M . A ., KOZA, S . M ., McCALL, S . A . e al.: Anal. Chem. 9, 2013, 6936‒6944.
HPLC-FLD/DAD DETERMINATION OF SALIVARY IMMUNE SYSTEM
ACTIVATION MARKERS, URIC ACID AND CREATININE IN CLINICAL
RESEARCH
VERNEROVÁ, A .,1,2 KUJOVSKÁ KRČMOVÁ, L.1,2
1 Depa men o Analy ical Chemis y, Facul y o Pha macy in H adec K álo é, Cha les Uni e si y,
Czech Republic
2 Depa men o Clinical Biochemis y and Diagnos ics, Uni e si y Hospi al H adec K álo é, Czech Republic
e-mail: e ne an@ a .cuni .cz

54
Neop e in, kynu enine and yp ophan a e use ul and impo an ma ke s o moni o ing
he ac i a ion o he immune sys em ha accompanies numbe o diseases such as in ec ion,
au oimmune and a ious malignan diseases . U ic acid (UA), he majo u ina y ni ogen-
con aining compound, is he p oduc o pu ine me abolism in he human body and impo an
an ioxidan wi h albumin and asco ba e in sali a . The main ad an ages o sali a as a diagnos ic
biological ma e ial a e simple, sa e, and non-in asi e collec ion . The new ch oma og aphic
me hod using monoli hic s a iona y phase o de e mina ion o neop e in, kynu enine, yp-
ophan, c ea inine, and UA in human sali a has been de eloped and will be p esen ed .
Neop e in and yp ophan we e de ec ed by luo escence de ec ion and c ea inine, kynu e-
nine, and UA by diode a ay de ec ion . Fil a ion as a simple and sui able sample ea men
p ocedu e o human sali a was used. This no el HPLC-FLD/DAD me hod in combina ion
wi h simple and as sample p epa a ion p ocedu e was used o es ing 56 eal sali a sam-
ples om pa ien s wi h cance (b eas , o a ian, colo ec al, and enal cance ) and 14 sali a
samples om pa ien s wi h pe iodon al diseases o moni o ea ly in lamma o y esponse.
The s udy was suppo ed by Minis y o Heal h o he Czech Republic – concep ual
de elopmen o esea ch o ganiza ion (UHHK, 00179906), by he Czech Heal h Resea ch
Council (P ojec . No. NV18-03-00130) and om he p ojec o Speci ic Academic Resea ch
(SVV 260 548).
Re e ences
1. NGAMCHUEA, K ., CHAISIWAMONGKHOL, K ., BATCHELOR-McAULEY, C . e al .: The Analys , 143,
2018, 81‒99.
DETERMINATION OF PLATINUM DRUGS IN HUMAN PLASMA
AFTER HYPERTHERMIC INTRAPERITONEAL CHEMOTHERAPY
TUROŇOVÁ, D.,1,2 KUJOVSKÁ KRČMOVÁ, L.1,2
1 Depa men o Analy ical Chemis y, Facul y o Pha macy in H adec K álo é, Cha les Uni e si y,
Czech Republic
2 Depa men o Clinical Biochemis y and Diagnos ics, Uni e si y Hospi al H adec K álo é, Czech Republic
e-mail: u ono d@ a .cuni .cz
Cy o educ i e su ge y combined wi h hype he mic in ape i oneal chemo he apy
(HIPEC) is a he apeu ic me hod ha maximally emo es he umou ollowed by in a-
ope a i e adminis a ion o a wa med chemo he apeu ic agen . The app oach aims a e o
maximize he an icance e ec and lowe chemo he apy’s sys emic side e ec s . In ape i-
oneal applica ion o chemo he apeu ics leads o hei dec eased le els in he bloods eam .1
The e o e we need o de elop mo e sensi i e me hods, which allow us o de ec he lowe
concen a ion o moni o he apeu ic le els and oxici y .
An HPLC-PDA me hod o he de e mina ion and quan i ica ion o cispla in o oxali-
pla in in he human plasma will be p esen ed . The aim o he me hod de elopmen was o
achie e a simple, as , and sensi i e me hod ha could be applied in s anda dly equiped
ou ine labo a o ies . As he de i a iza ion agen die hyldi hioca bama e (DDTC) was used .
55
The sepa a ion was ca ied ou in 4 .5 minu es using he C18 co e-shell column (100 ×
4 .6 mm, 2 .7 µm) combined wi h F5 column gua d . The mobile phase consis ed o ace oni-
ile and wa e , and he a ge analy e was de ec ed a 254 nm . The me hod is compensa ed
by applica ion o palladium chlo ide as he in e nal s anda d. The lowe limi o quan i ica-
ion o pla inum complexes was 20 ng mL−1 .
The s udy was suppo ed by Minis y o Heal h o he Czech Republic – concep ual
de elopmen o esea ch o ganiza ion (UHHK, 00179906), by he Czech Heal h Resea ch
Council (P ojec . No. NV18-03-00130) and om he p ojec o Speci ic Academic Resea ch
(SVV 260 548).
Re e ences
1. WITKAMP, A . J ., De BREE, E ., Van GOETHEM, A . R . e al.: Cance T ea . Re ., 27, 2001, 365‒374.
DEVELOPMENT OF UHPLC METHOD FOR ANALYSIS OF VITAMIN K
IN SERUM
MRŠTNÁ, K .,1,2 KUJOVSKÁ KRČMOVÁ, L.,1,2 MATYSOVÁ, L .1
1 Depa men o Analy ical Chemis y, Facul y o Pha macy in H adec K álo é, Cha les Uni e si y,
Czech Republic
2 Depa men o Clinical Biochemis y and Diagnos ics, Uni e si y Hospi al H adec K álo é, Czech Republic
e-mail: a nol ok@ a .cuni .cz
De e mina ion o i amin K, which plays an impo an ole in he human o ganism, is
a challenge in many aspec s o bioanalysis . Al hough i amin K is no cu en ly ou inely
analysed, in o ma ion on i s concen a ion in he human body is c ucial, mainly in e ms o
possible mani es a ions ela ed o i s de iciency. In he analysis o his i amin, i is a com-
mon p oblem o de ec i s low concen a ions . I is p esen only in nanomola concen a ions
in human bio luids. In addi ion o he low concen a ion, he e a e also obs acles such as i s
high pho osensi i i y, he ma ix in e e ence, and i s adhesion o plas ic and glass su aces .
The use o app op ia e sample p epa a ion in combina ion wi h ch oma og aphic analysis is
a solu ion o enabling he de e mina ion o pa icula o ms o i amin K .1
The p esen ed UHPLC me hod using luo escence de ec ion was de eloped o
de e mina ion o ou i amin K homologues (K1, MK4, MK7, MK9) in se um . The ch o-
ma og aphic sepa a ion was achie ed on Kine exTM C18 column (1.7 μm, 100 × 3 mm)
using g adien elu ion wi h me hanol/p opanol (phase B) and H2O (phase A). The low a e
was 0 .5 mL min−1 wi hin a o al un ime o 13 min . Cu en esul s o he me hod de elop-
men will be p esen ed .
The s udy was suppo ed by Minis y o Heal h o he Czech Republic – concep ual
de elopmen o esea ch o ganiza ion (UHHK, 00179906) and om he p ojec o Speci ic
Academic Resea ch (SVV 260 548).
Re e ences
1. SIMES, D . C ., VIEGAS, C . S . B ., ARAÚJO, N . e al .: Nu ien s, 12, 2020, a . 138 .
56
OPTIMIZATION OF CAPILLARY ELECTROPHORESIS AND SUPERCRITICAL
FLUID CHROMATOGRAPHY METHODS FOR THE SEPARATION
OF SILYMARIN
RIASOVÁ, P .,1,2 JÁČ, P.,1 POLÁŠEK, M .,1 VANDER HEYDEN, Y .,2 MANGELINGS, D .2
1 Depa men o Analy ical Chemis y, Facul y o Pha macy in H adec K álo é, Cha les Uni e si y,
Czech Republic
2 Depa men o Analy ical Chemis y, Applied Chemome ics and Molecula Modelling,
Facul y o Medicine and Pha macy, V ije Uni e si ei B ussel, Belgium
e-mail: iaso pe@ a .cuni .cz
Silybum ma ianum has been used since ancien imes o he ea men o a a ie y o
diso de s . The main ac i e cons i uen o he plan is silyma in, a mix u e o he s uc u ally
simila la onolignans silybin A and B, isosilybin A and B, silych is in, silydianin, and he
la onoid axi olin. The me hod op imiza ion p ocesses o he silyma in sepa a ion using
capilla y elec opho esis (CE) and supe c i ical luid ch oma og aphy (SFC) a e co e ed
in his s udy .
The CE me hod was op imized in e ms o concen a ion and pH o bo a e bu e , ype
and concen a ion o cyclodex in, o ganic modi ie con en , and capilla y leng h. Base-line
sepa a ion o all la onolignans was achie ed wi h a backg ound elec oly e con aining
100 mM bo ic acid o pH 9 .0, 5 mM hep akis(2,3,6- i-O-me hyl)-β-cyclodex in and 10%
( / ) MeOH in a 80.5/72 cm (50 µm id) used silica capilla y, a an applied ol age o
25 kV wi h UV de ec ion a 220 and 320 nm .
The SFC me hod was op imized on wo coupled-column sys ems . Expe imen al condi-
ions op imized du ing SFC me hod de elopmen we e modi ie ype and con en , low a e,
addi i es ype and concen a ion, backp essu e, column empe a u e and sample sol en .
Baseline sepa a ion o all compounds was no achie ed . The bes pe o ming me hod was
on a Lux Amylose-1 + Lux Cellulose-3 sys em, wi h he ollowing ch oma og aphic
condi ions: 40% MeOH wi h 0.1% ( / ) i luo oace ic acid, low a e 2.8 mL min−1 back-
p essu e 125 ba and column empe a u e 30 °C . The esolu ion o he c i ical peak pai s
silych is in and silydianin, and isosilybin B and A was 0 .85 and 0 .70, espec i ely .
The s udy was suppo ed by he Mobili y Fund o Cha les Uni e si y and om he p o-
jec o Speci ic Academic Resea ch (SVV 260 548).
NEW GRAPHENE BASED SORBENT FOR SOLID PHASE EXTRACTION
LOCHMAN, L., KUČERA, R.
Depa men o Pha maceu ical Chemis y and Pha maceu ical Analysis, Facul y o Pha macy
in H adec K álo é, Cha les Uni e si y, Czech Republic
e-mail: lochmanl@ a .cuni .cz
G aphene (G) is wo-dimensional sp2 single-a om- hick ca bon shee wi h hexagonal
s uc u e. High speci ic a ea ( heo e ical alue 2630 m2 g−1) and he a ini y o ca bon
57
ing s uc u es ia π-π s acking in e ac ions make G and g aphene oxide (GO) p omis-
ing candida es o applica ion in analy ical chemis y .1 Se e al s udies used GO o G o
p epa a ion o he new so ben s o SPE o SPME, and ma e ials wi h imp o ed p ope ies
we e p esen ed .2‒4
The aim o ou p ojec is o y o p epa e a new al e na i e so ben based on g aphene .
The wo k is ocused on he modi ica ion o he i anium oxide pa icles (Zi Ch om-SAX)
by g aphene . Tha will be ollowed by he s udy o so ben e en ion on he mix u e o
model analy es (e.g ., ibup o en, lidocaine, p opylpa aben, me op olol) wi h di e en acid-
base p ope ies. Such kind o ma e ial is p esen ed o he i s ime.
Ob ained esul s will be compa ed wi h he p ope ies o unmodi ied pa icles and GO
o G in ee o m . The quali y o pa icle coa ing oge he wi h e en ion pe o mance will
be discussed .
The s udy was suppo ed by he Resea ch p og amme De elopmen and S udy o D ugs
(P og es Q42) and om he p ojec o Speci ic Academic Resea ch (SVV 260 547).
Re e ences
1. RAO, C . N . R ., SOOD, A . K . (eds .): G aphene: Syn hesis, P ope ies, and Phenomena . Weinheim, Wiley-VCH,
2013 .
2. LIU, Q ., SHI, J ., SUN, J . e al.: Angew. Chem., 50, 2011, 5913‒5917.
3. HUANG, K .-J ., JING, Q .-S ., WEI, C .-Y . e al .: Spec ochim . Ac a, Pa A: Molecula and Biomolecula Spec-
oscopy, 79, 2011, 1860‒1865.
4. LI, N ., CHEN, J ., SHI, Y .-P.: Talan a, 191, 2019, 526‒534.
DIRECT ELECTROMEMBRANE EXTRACTION OF ANTHRACYCLINES
FROM TISSUE SAMPLES
BAVLOVIČ PISKÁČKOVÁ, H.,1 KOLLÁROVÁ-BRÁZDOVÁ, P .,2 ŠTĚRBA, M.,2 KUČERA, R.,1
ŠTĚRBOVÁ-KOVAŘÍKOVÁ, P.1
1 Depa men o Pha maceu ical Chemis y and Pha maceu ical Analysis, Facul y o Pha macy
in H adec K álo é, Cha les Uni e si y, Czech Republic
2 Depa men o Pha macology, Facul y o Medicine in H adec K álo é, Cha les Uni e si y, Czech Republic
e-mail: piskacha@ a .cuni .cz
Tissue analysis p esen s bioanaly ical challenge compa ed o analysis o liquid bio-
logical samples . Fi s ly, homogeniza ion p io sample ea men is equi ed o ensu e
bo h ep esen a i e sample and e ec i e sample ex ac ion. Fu he di icul y is de e mi-
na ion o analy e ex ac abili y, as he spiked issue sample o e en spiked homogena e
do no exac ly mimic d ug binding and dis ibu ion in in ac issue . Elec omemb ane
ex ac ion (EME) is a hyb id mic oex ac ion echnique laying be ween liquid-liquid
ex ac ion (LLE) and elec opho esis . The ex ac ion o cha ged analy es is pe o med
om he aqueous sample h ough he wa e immiscible o ganic suppo ed liquid mem-
b ane (SLM) o he accep o solu ion . The d i ing o ce o he ex ac ion is an elec ical
po en ial, which is applied ac oss he SLM . The aim o his s udy was o op imize he
EME o isola ion o an h acyclines (ANT) om issues (li e , hea and skele al mus-
64
COMPARISON OF IMPURITY PROFILES IN LEVOTHYROXINE TABLETS
USING METABOLOMICS BASED UHPLC-HRMS METHOD
CATAPANO, M . C .,1 HRUŠKOVÁ, A .,1 GARRIGUES, J . C .,2, NOVÁKOVÁ, L .1
1 Depa men o Analy ical Chemis y, Facul y o Pha macy in H adec K álo é, Cha les Uni e si y,
Czech Republic
2 Labo a oi e I .M .R .C .P, Uni e si é Toulouse III-Paul Saba ie , Toulouse, F ance
e-mail: ca apanm@ a .cuni .cz
The aim o his s udy was o iden i y impu i ies in se e al o mula ions o able s
con aining le o hy oxine using an UHPLC-HRMS me abolomics-based me hod and o
compa e he p o iles o known and unknown impu i ies. These impu i ies may be ela ed
o he epo ed side-e ec s o le o hy oxine able s . In pa icula , he me hod was ocused
on (1) he iden i ica ion o known and unknown impu i ies (molecula o sup amolecu-
la ) om he ac i e p inciple ing edien (API) and om he excipien s, such as manni ol,
lac ose, and s ea ic acid, (2) o he s udy o molecula in e ac ions be ween API and he
excipien s .
An impo an pa o his s udy was he compa ison o di e en me abolomics wo k-
lows including expe imen al design, da a analysis, ea u e de ec ion (peak picking),
s a is ical e alua ion, and compound iden i ica ion. Analysis o le o hy oxine samples
unde wen andomiza ion p ocess in o de o p e en echnical/ins umen al biases.
Th ee di e en expe imen al designs we e compa ed in e ms o sample p epa a ion and
UHPLC-HRMS analysis . Da a p ocessing in ol ed es ing o di e en se ings (mass
accu acy, h esholds) as well as es ing di e en so wa e pla o ms .
The da a we e acqui ed in MS ull scan mode, bo h ESI nega i e and posi i e mode,
and will be used in bo h a ge ed and non- a ge ed da a p ocessing . In a ge ed analysis we
con i med he p esence o manni ol s ea a e in le o hy oxine d ug o mula ions con ain-
ing manni ol as an auxilia y ing edien . I was also possible o iden i y some impu i ies,
o example le o hy oxine-lac ose adduc s (MW = 1100 .7923) . On he o he hand, he
p esence o sup amolecula le o hy oxine-manni ol complex and le o hy oxine-manni ol
adduc was no con i med in o mula ions. In he nex s ep, mo e unknown impu i ies will
be iden i ied, and non- a ge ed me abolomics will be applied.
The s udy was suppo ed by EFSA-CDN (Reg. No. CZ.02.1.01/0.0/0.0/16_019/0000841)
co- unded by ERDF and om he p ojec o Speci ic Academic Resea ch (SVV 260 548).
EXTRACTION OF PHENOLIC COMPOUNDS FROM EUCALYPTUS LEAVES
USING SUPERCRITICAL FLUID EXTRACTION COUPLED WITH LIQUID
CHROMATOGRAPHY/TANDEM MASS SPECTROMETRY
HASHEMI, B., PILAŘOVÁ, V., NOVÁKOVÁ, L.
Depa men o Analy ical Chemis y, Facul y o Pha macy in H adec K álo é, Cha les Uni e si y,
Czech Republic
e-mail: hashemib@ a .cuni .cz

65
Supe c i ical luid is a iable al e na i e ex ac ion sol en o bioac i e compounds
om hei na u al sou ces such as plan s, ui s, and lowe s. Ca bon dioxide is commonly
used as supe c i ical sol en o ex ac a wide ange o non-pola o mid pola compounds .
Di e en pa s o eucalyp us ee including lea es, ba k, and s ems con ain bo h ola ile
and non- ola ile bioac i e compounds ha ha e been widely u ilized in pha maceu ical
and cosme ic indus ies. In he i s pa o he p esen wo k, supe c i ical luid ex ac-
ion (SFE) using e hanol as he co-sol en is used o he ex ac ion o di e en phenolic
compounds including phenolic acids and la onoids om eucalyp us lea es ollowed by
he analysis o he ex ac ed analy es using ul a-high pe o mance liquid ch oma og aphy/
andem mass spec ome y (UHPLC-MS/MS). In he p oposed me hod, he pa ame e s as-
socia ed wi h he UHPLC-MS/MS we e in es iga ed and op imized i s and hen ac o s
a ec ing SFE p ocess will be assessed as well . The elec osp ay ioniza ion (ESI) pa ame-
e s we e op imized in bo h ioniza ion modes. MS/MS was pe o med on iple quad upole
and selec ed eac ion moni o ing (SRM) was de eloped o quan i a i e analysis o he a -
ge phenolics . The calib a ion cu es we e p epa ed o check he linea concen a ion ange
and sensi i i y. The ob ained SFE ex ac was analyzed using he de eloped UHPLC-MS/
MS and di e en phenolic acids (such as p o oca echuic acid, gallic acid, ca eic acid, and
chlo ogenic acid) and la onoids (including ca echin, axi olin, phlo idzin, and que ci in)
we e iden i ied among he ex ac ed compounds om eucalyp us lea es. In he second
s age, we plan o de elop supe c i ical luid ch oma og aphy andem mass spec ome y
(SFC-MS/MS) me hod which would include he analysis o bo h ola ile and phenolic
compounds ex ac ed om eucalyp us lea es .
The s udy was suppo ed by EFSA-CDN (Reg. No. CZ.02.1.01/0.0/0.0/16_019/0000841)
co- unded by ERDF and om he p ojec o Speci ic Academic Resea ch (SVV 260 548).
THE DEVELOPMENT OF EXTRACTION METHOD USING SUPERCRITICAL
FLUIDS
HOLLÁ, M., KHOLOVÁ, A., SKLENÁŘOVÁ, H., ŠATÍNSKÝ, D.
Depa men o Analy ical Chemis y, Facul y o Pha macy in H adec K álo é, Cha les Uni e si y,
Czech Republic
e-mail: hollama@ a .cuni .cz
Recen ly, g owing in e es in using g een echnologies o he ex ac ion o aluable
compounds wi h an ioxidan p ope ies has been obse ed . Ex ac ions u ilizing ca bon
dioxide belong o his g oup . By applying p essu e and mild empe a u e abo e he c i ical
poin o liquid CO2 o a mix u e o CO2 and mo e pola co-sol en (e hanol, me hanol,
wa e ), a supe c i ical luid is o med. Supe c i ical luids a e cha ac e ized by highe di u-
si i y, lowe densi y, iscosi y and su ace ension . This app oach enables he ex ac ion o
plan polyphenols unde mild condi ions and wi hou he use o oxic sol en s . Mo eo e ,
ex ac ions a e pe o med in he absence o ligh and ai du ing ex ac ion . Thus, he isk
o deg ada ion eac ions is minimized .
66
In his ongoing s udy, we aim o de elop an ex ac ion me hod o he ex ac ion o
polyphenols om d ied apples . Since mos o he polyphenols ypically p esen in apples
a e pola , pola co-sol en is needed . Fo he e alua ion o selec ed analy es (gallic acid,
chlo ogenic acid, epica echin, u in, phlo idzin, phlo e in, que ce in, que ci in, ca echin,
ca eic acid), he newly de eloped UHPLC-DAD me hod was used .
In his con ibu ion, he in luence o he main es ed pa ame e s on he ex ac ion e-
co e y will be discussed . The op imiza ion o SFE was di ided in o wo main pa s . The
Modde so wa e was used o he p epa a ion o he expe imen al design . Fi s , Placke
Bu man design was used o iden i y he mos signi ican ac o s (p essu e, empe a u e,
wa e con en in e hanolic co-sol en , CO2/co-sol en a io). Second, he cen al composi e
design was applied as he second s ep . A his poin , a na owe ange o main ac o s was
u he op imized. The ixed alues o mino ac o s we e chosen ega ding he highes
eco e ies o a ge analy es. The s udy will con inue wi h ex ac ion kine ics and he in lu-
ence o glass beads size on ex ac ion eco e y .
The s udy was suppo ed by he G an Agency o Cha les Uni e si y (P ojec
No. 1466119) and om he p ojec o Speci ic Academic Resea ch (SVV 260 548).
SEPARATION POTENTIAL OF CHROMATOGRAPHIC METHODS
IN THE ANALYSIS OF STRUCTURALLY SIMILAR STEROIDS
GAZÁRKOVÁ, T., HROMÁDKO, J., KOČOVÁ VLČKOVÁ, H., NOVÁKOVÁ, L.
Depa men o Analy ical Chemis y, Facul y o Pha macy in H adec K álo é, Cha les Uni e si y,
Czech Republic
e-mail: gaza ko a@ a .cuni .cz
The ull ch oma og aphic sepa a ion o a complex g oup o isome ic and isoba ic s e -
oids emains a complica ed analy ical challenge, e en hough GC-MS/MS and LC-MS/
MS echniques a e well es ablished in hei analysis . The analyzed compounds di e only
by mino s uc u al modi ica ions. Mo eo e , a ypical loss o one o h ee wa e molecules
in he MS spec a leads o he o ma ion o addi ional isoba s . To elimina e he obse ed
in e e ences and co ec ly quan i y he a ge analy es, i is necessa y o achie e ull ch o-
ma og aphic sepa a ion .
The p esen s udy aims a he de elopmen and op imiza ion o as and sensi i e UH-
PLC-MS/MS and UHPSFC-MS/MS me hods o he analysis o 37 s e oids. The analyzed
compounds belong o he C19 and os enes, C21 p egnanes, and syn he ic s e oid g oups
and gene a e 11 c i ical pai s/g oups o analy es due o hei s uc u al simila i y. The e-
o e, he sepa a ion po en ial o bo h ch oma og aphic me hods will be examined in de ail
and compa ed .
Comp ehensi e sc eening o s a iona y phases was ca ied ou using gene ic g adien
elu ion in bo h ch oma og aphic me hods, UHPSFC and UHPLC . A sc eening o mobile
phases and g adien op imiza ion ollowed in he nex s ep using he s a iona y phases
wi h he mos success ul sepa a ion o c i ical pai s . Biological samples o mouse plasma
we e ob ained om he Czech Academy o Sciences, dealing wi h he p ojec ocused on
67
he in es iga ion o changes in le els o exp essed s e oids due o ch onic s ess exposu e .
Hence, he p o ein p ecipi a ion me hod was de eloped o a a ge ma ix . Mo eo e , he
physiological le els o some s e oids in he plasma make a quan i ica ion me hod e en
mo e challenging. Finally, he PP-UHPLC-MS/MS me hod was selec ed o alida ion and
he analysis o biological samples .
This s udy was suppo ed by he STARSS p ojec (Reg. No. CZ.02.1.01/0.0/0.0/15_003
/0000465) co- unded by ERDF and om he p ojec o Speci ic Academic Resea ch (SVV
260 548).
AUTOMATED PROCEDURES BASED ON HOMOGENEOUS LIQUID-LIQUID
EXTRACTION AND PROTEIN PRECIPITATION USING LAB-IN-SYRINGE
APPROACH
FIKAROVÁ, K., HORSTKOTTE, B., MACHIÁN, D., SKLENÁŘOVÁ, H.
Depa men o Analy ical Chemis y, Facul y o Pha macy in H adec K álo é, Cha les Uni e si y,
Czech Republic
e-mail: [email p o ec ed]
We epo on he de elopmen o wo new Lab-In-Sy inge (LIS)-au oma ed sal ing-ou
liquid-liquid ex ac ion (SALLE) me hods, one in combina ion wi h online solid-phase ex-
ac ion (SPE), coupled o liquid ch oma og aphy (LC) . In bo h cases, SALLE was ca ied
ou in he oid o he sy inge including a magne ic s i ing ba o on-demand homogenous
mixing and using ace oni ile as an ex ac ion sol en miscible wi h wa e . A sa u a ed sal
solu ion o magnesium sul a e and sodium chlo ide was used o induce phase sepa a ion .
This me hodology is sui able o he ex aci on o mode a ely pola compounds, in ou
wo k, sul onamide chemo he apeu ics . The ad an age o he p ocedu e is he compa ibili y
o he used sol en wi h LC . On he o he hand, only small p econcen a ion ac o can
be achie ed as phase sepa a ion can be achie ed o app oxima ely balanced olumes o
o ganic and aqeuous phase .
To imp o e bo h p econcen a ion ac o and ex ac clean-up, in he i s wo k, he
ex ac was dilu ed in-sy inge wi h alkaline bu e and he analy es we e apped a pH 10
on an anion-exchange esin ca idge in eg a ed in o he LC injec ion loop, hus achie ing
a double-s age and o hogonal sample clean-up . Analy es we e elu ed om he ca idge
by he acidic mobile phase in g adien elu ion mode . Running he sepa a ion o he ana-
ly es and he wo-s ep p epa a ion o he ollowing sample in pa allel allowed educing
he o al ime o analysis o 13 .5 min . The me hod was applied o spiked u ine samples
yielding an a e age eco e y alue o 102 .7 ± 7 .4% and limi s o de ec ion a low ppb
le el .
A simila p ocedu e can be used o cen i uga ion-less dep o eina ion o milk samples .
In his case, ace oni ile also ac s as a p ecipi a ing agen . The addi ion o sal hen sepa-
a es h ee phases: an o ganic ex ac wi h p econcen a ed analy e, p ecipi a ed p o eins,
and he aqueous sample and sal solu ion mix u e . Fi s op imiza ion esul s om his s udy
will be p esen ed .
68
The s udy was suppo ed by he STARSS p ojec (Reg. No. CZ.02.1.01/0.0/0.0/15_003
/0000465) co- unded by ERDF and om he p ojec o Speci ic Academic Resea ch (SVV
260 548).
MAGNETIZATION OF COMMERCIAL HLB PARTICLES FOR AUTOMATIC
IN-SYRINGE DISPERSIVE MICRO-SOLID PHASE EXTRACTION OF SURFACE
WATER CONTAMINANT
GEMUH, C . V ., HORSTKOTTE, B ., SOLICH, P .
Depa men o Analy ical Chemis y, Facul y o Pha macy in H adec K álo é, Cha les Uni e si y,
Czech Republic
e-mail: gemuhc@ a .cuni .cz
We p esen a simple app oach o magne ic dispe si e solid phase mic oex ac ion and
i s au oma ion o he en ichmen o wa e con aminan s . SupelTM-Selec HLB (hyd ophilic
modi ied s y ene polyme ) beads we e magne ized by in oducing magne i e nanopa icles
(Fe3O4) in o he so ben . Fo his, he beads we e soaked wi h FeCl2 and FeCl3 and hen
washed wi h NH4OH leading o he p ecipi a ion o magne i e nanopa icles inside he
so ben as epo ed elsewhe e .1 The so- unc ionalized so ben was used in a dispe si e sol-
id phase ex ac ion me hodology ha was au oma ed using he Lab-In-Sy inge echnique .
The me hodology ollowed a p e ious s udy on using magne ic nanopa icles .2 In sho ,
sample and bead suspension a e aspi a ed in o he sy inge oid and dispe sed by he aid o
a magne ic s i ing ba placed inside he sy inge . By au oma ic ac i a ion and deac i a ion
o magne ic s i ing p ocess, he analy es we e cap u ed by he dispe sed so ben beads and
hen e ained on he s i ing ba ha allowed disca ding he sample solu ion a e he phase
sepa a ion. The ea e , he eluen o 60 : 40 ( / ) ace oni ile : ammonium phospha e bu e
was used o elu e he analy es o in e es . This ex ac ion sys em was coupled online o
a liquid ch oma og aphy ins umen o he de e mina ion o model analy es mebendazole,
bisphenol A, benzyl 4-hyd oxybenzoa e, diclo enac and i gasan . Essen ial pa ame e s such
as ex ac ion ime, elu ion ime, composi ion and olume o eluen , as well as phase sepa a-
ion ime we e op imized . The de eloped me hod will be implemen ed o he analysis o
he model con aminan s in su ace wa e (lakes and i e s) .
The s udy was suppo ed by he G an Agency o Cha les Uni e si y (P ojec
No. 1070120) and om he p ojec o Speci ic Academic Resea ch (SVV 260 548).
Re e ences
1. FRESCO-CALA, B ., CÁRDENAS, S ., VALCÁRCEL, M .: J . Ch oma og . A, 1468, 2016, 55–63 .
2. MAYA, F ., CABELLO, C . P ., ESTELA, J . M . e al .: Anal . Chem ., 87, 2015, 7545–7549 .
69
WHAT WE CAN AND CANNOT EXPECT FROM EXTRACTION
ON NANOFIBROUS SORBENTS?
RAABOVÁ, H .,1 HÁKOVÁ, M .,1 ERBEN, J .,2 ŠATÍNSKÝ, D.1
1 Depa men o Analy ical Chemis y, Facul y o Pha macy in H adec K álo é, Cha les Uni e si y,
Czech Republic
2 Depa men o Nonwo ens and Nano ib ous Ma e ials, Facul y o Tex ile Enginee ing,
Technical Uni esi y o Libe ec, Czech Republic
e-mail: aabo ah@ a .cuni .cz
G ea in e es in inno a i e so p ion ma e ials o solid-phase ex ac ion has b ough
nano ib ous polyme s o he scien i ic scope. Ou esea ch g oup’s knowledge abou
nano ib ous polyme s gained o e yea s, esul ed in he s udy whe e he nano ib ous
ex ac ion mechanism is discussed . The eigh polyme s we e es ed as ex ac ion so ben s
o ace ylsalicylic acid, moxonidine, me op olol, p op anolol, p opa enone, dil iazem,
a o as a in, and amioda one p esen in 3 ma ixes, including an o ganic sol en , hu-
man se um, and bo ine se um albumin . The ex ac ion was ca ied ou in an ex ac ion
ca idge manually illed wi h nano ibe s and online coupled wi h a high-pe o mance
liquid ch oma og aphy sys em ia a six-po swi ching al e . The ob ained ex ac ion
eco e ies we e used o he e alua ion o analy e e en ion on indi idual so ben s . The
main aim o his s udy was o de e mine how his e en ion is a ec ed by analy e phys-
icochemical p ope ies and ma ix complexi y . This unde s anding should lead o a mo e
conscious applica ion o nano ib ous so ben s in ex ac ion echniques and simpli ied
me hod de elopmen .
As we ound ou , he es ed polyme s p o ided high ex ac ion e iciency o he com-
pounds wi h log P exceeding 2. I was also con i med ha lipophilici y is he majo d i ing
o ce in he e en ion mechanism . Mo eo e , by di ec injec ion o spiked bo ine se um
albumin and human se um ma ix on nano ibe s, some o hem con i med hei po en ial
o ex ac analy e and emo e p o ein mac omolecules in one s ep .
The s udy was suppo ed by he STARSS p ojec (Reg. No. CZ.02.1.01/0.0/0.0/15_003/
0000465) co- unded by ERDF, by he Czech Science Founda ion (P ojec No. 20-19297S),
by he G an Agency o Cha les Uni e si y (P ojec No. 766218) and om he p ojec o
Speci ic Academic Resea ch (SVV 260 548).
MODERN SORBENTS IN ONLINE SOLID PHASE EXTRACTION COUPLED
TO LIQUID CHROMATOGRAPHY FOR DETERMINATION OF BISPHENOLS
IN MILK
KHOLOVÁ, A., RAABOVÁ, H., LHOTSKÁ, I., ŠATÍNSKÝ, D.
Depa men o Analy ical Chemis y, Facul y o Pha macy in H adec K álo é, Cha les Uni e si y,
Czech Republic
e-mail: kholo aa@ a .cuni .cz

70
Va ious ad anced so ben s o online ex ac ion and de e mina ion o bisphenol A,
bisphenol AF, bisphenol C, bisphenol A diglycidyl e he , and bisphenol F diglycidyl e he
in bo ine milk samples ha e been compa ed . The milk is a complex ma ix con aining
p o eins and lipids . Ou app oach o sample p epa a ion p esen s a new online me hod
including as ex ac ion using p ecolumn coupled o liquid ch oma og aphy wi h luo-
escence de ec ion. Fi e ypes o ib ous so ben s, including polye hylene mic o ibe s,
polyp opylene mic o ibe s, polycap olac one mic o ibe s/nano ibe s composi e, polycap-
olac one mic o ibe s/poly inylidene di luo ide nano ibe s composi e, and polyamide 6,
we e compa ed in e ms o ex ac ion and clean-up e iciency wi h comme cially a ail-
able molecula ly imp in ed polyme s o bisphenols and es ic ed access media so ben
RP-18 ADS. The polyme ibe s illed in a ca idge and also comme cial so ben s we e
di ec ly connec ed o he HPLC sys em and he clean-up s ep and he subsequen ch oma-
og aphy sepa a ion op imized . The sepa a ion was ca ied ou using analy ical column
YMC-T ia C18 ExRS (150 × 4.6 mm, pa icle size 3 µm) ollowed by luo escence
de ec ion (Ex 273 nm, Em 300 nm) . Sol en s sui able o sepa a ion we e ace oni ile
wi h wa e unde g adien elu ion, o ex ac ion 15% me hanol, and he o al low a e o
1 .0 mL min−1 was used . The so ben s wi h he bes esul s we e used o con ol o bisphe-
nol con amina ion in milk packed in plas ic bo les . The measu ed esul s we e compa ed
wi h he mig a ion limi es ablished by he Eu opean Union o BPA 0 .05 mg kg−1 in ood
con ac plas ics .
The s udy was suppo ed by he STARSS p ojec (Reg. No. Z.02.1.01/0.0/0.0/15_003/
0000465) co- unded by ERDF, by he Czech Science Founda ion (P ojec No. 20-19297S),
by he G an Agency o Cha les Uni e si y (P ojec No. 1134119) and om he p ojec o
Speci ic Academic Resea ch (SVV 260 548).
DETERMINATION OF PHENOLIC PROFILE IN FRUIT TREES
DURING VEGETATION PERIOD
ADAMCOVÁ, A., ŠÍROVÁ, K., ŠILHAVÁ, K., ŠATÍNSKÝ, D.
Depa men o Analy ical Chemis y, Facul y o Pha macy in H adec K álo é, Cha les Uni e si y,
Czech Republic
e-mail: adamcoa1@ a .cuni .cz
The aim o he s udy was o de e mine a spec um o phenolic compounds and hei
con en in apple and pea ee ma e ial – lea es, ba k, buds, blossom, and ui . The me ha-
nol ex ac s we e ob ained om aw ma e ial o di e en cul i a s . The main ex ac ed
phenolic compounds om apple (phlo idzin, phlo e in, chlo ogenic acid, and que ce in)
and pea (a bu in, u in, chlo ogenic acid and i s de i a i es) ee ma e ial we e analyzed
by wo di e en alida ed high pe o mance liquid ch oma og aphy me hods . Finally,
YMC-T ia C18 ExRS 150 × 4.6 mm, pa icle size 5 μm, po e size 8 nm (apple ee) and
ASCENTIS Exp ess RP-Amide 150 × 4.6 mm, pa icle size 2.7 μm (pea ee) analy ical
columns we e used o analysis . Column empe a u e was 30 °C and injec ion olume
was 1 μl. The sepa a ion was pe o med wi h g adien elu ion a low a e 1 mL min−1 .
71
The mobile phase consis ed o ace oni ile and 0 .1% phospho ic acid . The de ec ion was
ca ied ou wi h diode a ay de ec o . To obse e changing phenolic p o ile, sampling was
pe o med in Ma ch, June, Augus , and No embe du ing he yea s 2019 and 2020 . The
highes concen a ion o bioac i e compounds was ound in lea es ollowed by buds in
sp ing season in bo h ypes o s udied ees . In ha season, he concen a ion ange was
om 164 .25 mg g−1 o 228 .85 mg g−1 in 10 apple ee cul i a s and om 85 .04 mg g−1 o
161 .69 mg g−1 in 10 pea ee cul i a s . The main phenolic compounds we e phlo idzin
in apple ees, and a bu in and chlo ogenic acid in pea ees. This inding can lead o ap-
plying ui ee ma e ial as a enewable esou ces o ood supplemen s o ex ac s wi h
bene icial e ec o human heal h.
The s udy was suppo ed by he Technology Agency o he Czech Republic (P ojec
No. TJ02000196), by he G an Agency o Cha les Uni e si y (P ojec No. 1152120) and
om he p ojec o Speci ic Academic Resea ch (SVV 260 548).
ADVANCED CHROMATOGRAPHIC APPROACH IN PHENOLIC COMPOUNDS
PROFILING IN ARCHIVE TOKAJ WINES
MORAVCOVÁ, P .,1 ŠPÁNIK, I .,2 MACHYŇÁKOVÁ, A.,2 ŠATÍNSKÝ, D.1
1 Depa men o Analy ical Chemis y, Facul y o Pha macy in H adec K álo é, Cha les Uni e si y,
Czech Republic
2 The Ins i u e o Analy ical Chemis y, Facul y o Chemical and Food Technology, Slo ak Uni e si y
o Technology in B a isla a, Slo akia
e-mail: mo a copa@ a .cuni .cz
The p esen ed expe imen is ocused on he cha ac e is ics o a chi e Tokaj wines,
especially in e ms o hei bene i s o human body in he o m o an ioxidan ac i i y o
phenolic compounds .1 The samples o a chi e Tokaj wine come om ineya ds o he
Slo ak pa o he Tokaj wine egion . The Tokaj wine egion is one o he ew a eas wi h
a p oduc ion o special wine made om g apes a ec ed by noble o Bo y is cine ea
unde pa icula en i onmen al condi ions, which leads o he p oduc ion o na u al wines
wi h a unique a oma .2 Mo e han 60 a chi e samples we e e alua ed in e m o phenolic
subs ances p o ile, including hyd oxybenzoic and hyd oxycinnamic acids, s ilbenes and
la an-3-ols. Eigh een phenolic compounds we e iden i ied. Indi idual phenolic subs anc-
es, which di e signi ican ly in hei physico-chemical p ope ies, we e de ec ed by ul a
high pe o mance liquid ch oma og aphy me hod wi h diode a ay de ec ion . Sepa a ion
and quan i ica ion we e inally conduc ed on a pola C18 column wi h co e-shell pa icles
(150 mm × 3.0 mm, pa icle size 2.6 µm) using a g adien elu ion mode a a low a e o
1 .0 mL min‒1 wi h a mobile phase consis ing o ace oni ile and 0 .1% phospho ic acid a
50 °C . These sepa a ion condi ions p o ided eliable alida ion esul wi h linea i y (R >
0 .9996), p ecision (CV < 3 .91%), eco e y (87 .35–118 .67%), which a e conside ed ac-
cep able o applica ion in he cha ac e iza ion o hese ypes o ma ices .
The s udy was suppo ed om he p ojec o Speci ic Academic Resea ch (SVV 260 548).
72
Re e ences
1. STAŠKO, A ., POLOVKA, M ., BREZOVÁ, V . e al .: Food Chem ., 96, 2006, 185–196 .
2. MAGYAR, I .: Ad . Food Nu . Res ., 63, 2011, 147–206 .
A VALIDATED UHPLC METHOD FOR THE DETERMINATION
OF CAFFEOYLQUINIC AND DI-CAFFEOYLQUINIC ACIDS IN GREEN COFFEE
EXTRACTS USING AN RP-AMIDE FUSED-CORE COLUMN
MAJOROVÁ, M., FIBIGR, J., ŠATÍNSKÝ, D.
Depa men o Analy ical Chemis y, Facul y o Pha macy in H adec K álo é, Cha les Uni e si y,
Czech Republic
e-mail: majo o mic@ a .cuni .cz
The aim o he s udy was o de elop and alida e new UHPLC me hod o de e mina-
ion o chlo ogenic acids and hei di-subs i u ed de i a es in nu aceu icals con aining he
ex ac o g een co ee beans . The de eloped and alida ed UHPLC me hod was used o
de e mina ion o chlo ogenic acids in nu aceu icals Kilos op (As ina Pha m, a .s .), Zelená
ká a Ex a (Medicu a Na u al), Maxi i alis Zelená ká a (Simply You Pha maceu icals),
Vies e Zelená ká a P emium (Vol Re ail), Zelená ká a bylinný ex ak (Top e ), Zelená
ká a (Vi o Li e), and Kyselina chlo ogeno á (Vi o Li e) . Fo he analysis, ex ac s we e
ob ained om he samples o nu aceu icals, using me hanol and 5% aqueous o mic acid
solu ion (25 : 75, / ). Ex ac s we e il a ed h ough 0.22 µl PTFE il e s. The analysis,
which p o ided sa is ying sepa a ion o all de i a i es o chlo ogenic acid, was pe o med
on he Ascen is Exp ess® RP-Amide (100 × 2.1 mm, pa icle size 2.7 μm) ch oma og aphy
column using g adien elu ion p og am wi h mobile phase consis ed o mix u e o ace oni-
ile and 5% aqueous solu ion o o mic acid. The sepa a ion was pe o med a low a e
o 0 .9 mL min‒1 and he de ec ion was ca ied ou a wa eleng h o 325 nm using PDA
de ec o . The column empe a u e was 30 °C . Acco ding o he s udy, in g een co ee bean
ex ac samples, chlo ogenic acid was ound as majo componen . This esea ch e ealed
ha g een co ee bean ex ac s a e ich sou ce o chlo ogenic acids . Howe e , he quali y
o he es ed p epa a ions in e m o chlo ogenic acid con en widely di e ed acco ding o
he p oduce .
The s udy was suppo ed om he p ojec o Speci ic Academic Resea ch (SVV 260 548).
73
BIOCHEMISTRY, PHARMACOLOGY AND TOXICOLOGY SECTION
A PREDICTIVE CAPABILITY OF 3D PRIMARY HUMAN HEPATOCYTE
SPHEROIDS IN DRUG-DRUG INTERACTIONS
SMUTNÝ, T ., PÁVEK, P .
Depa men o Pha macology and Toxicology, Facul y o Pha macy in H adec K álo é, Cha les Uni e si y,
Czech Republic
e-mail: smu 6aa@ a .cuni .cz
D ug-d ug in e ac ions (DDIs) ep esen a se ious medical conce n being associa ed
wi h a ea men ailu e o oxici y . CYP3A4 is among he mos impo an d ug-me abo-
lizing enzymes (DMEs) as i is in ol ed in bio ans o ma ion o app oxima ely 50% o all
ma ke ed d ugs . Add essing a capaci y o d ug candida es o induce CYP3A4 unc ion in
d ug de elopmen is a p e equisi e o he apeu ic success and pa ien sa e y .
P ima y human hepa ocy es (PHHs) cul u ed in 2D monolaye a e a gold s anda d o
pe o m CYP induc ion s udies ecommended by egula o y agencies . PHHs, howe e , un-
de go d ama ic dedi e en ia ion a e seeding losing signi ican ly hei me abolic capaci y.
In con as , 3D sphe oids o PHHs gene a ed on ul a-low adhe en pla es ha e been shown
o closely mimic physiological pheno ype o human li e issue . Mo eo e , 3D model can
main ain s able exp ession o DMEs o a ew weeks enabling o s udy a long- e m e ec
o d ugs on DME exp ession pa e n .
I my alk, I am going o add ess a ole o 3D sphe oids in a sc eening o CYP3A4 in-
duce s pu ing emphasize on bene i s o 3D PHH sys em such as a high and s able basal
exp ession o CYP3A4 . The limi s o in i o- o-in i o ansla ion accu acy o CYP3A4
induc ion in 2D compa ed o 3D PHH model will be demons a ed on a case o AZD1208
d ug candida e . Ou in-house expe ience wi h 3D sphe oids will be also discussed .
The s udy was suppo ed by EFSA-CDN (Reg. No. CZ.02.1.01/0.0/0.0/16_019/0000841)
co- unded by ERDF and om he p ojec o Speci ic Academic Resea ch (SVV 260 549).
MURINE CONSTITUTIVE ANDROSTANE RECEPTOR (CAR) LIGAND TCPOBOP
INDUCED HEPATOMEGALY IN HUMANIZED CAR MICE IS INDEPENDENT
OF CAR ACTIVATION
ŠKODA, J ., DUŠEK, J ., PÁVEK, P .
Depa men o Pha macology and Toxicology, Facul y o Pha macy in H adec K álo é, Cha les Uni e si y,
Czech Republic
e-mail: skodajo@ a .cuni .cz
TCPOBOP – 1,4-bis[2-(3,5-dichlo opy idyloxy)]benzene – is a widely-used p o o ype
cons i u i e and os ane ecep o (CAR, N 1i3) ligand . In mice, TCPOBOP a e CAR ac-
80
Pho odynamic he apy is a highly speci ic and clinically app o ed he apeu ic p oce-
du e o cance ea men based on he p oduc ion o cy o oxic eac i e oxygen species
upon he ligh ac i a ion o an o he wise non oxic pho osensi ize . Fo his p ojec , he
no el pe iphe ally c owded ca ionic ph halocyanines (Pcs) con aining 8 o 16 py idyl moi-
e ies (neu al o qua e nized) we e syn hesized and hei pho odynamic p ope ies we e
u he e alua ed in de ail .
Pho odynamic ac i i y was demons a ed on se e al cell lines – malignan (HeLa and
MCF-7) and non-malignan (3T3 and EA .hy926) . The esul s o indi idual in i o expe i-
men s ha e shown e y high pho o oxici y wi h EC50 up o 47 nM (MCF-7 cells) a e
i adia ion while main aining desi ably low inhe en oxici y (in he da k), wi h TC50 >
600 000 nM . The Pcs we e localized in acellula ly, p ima ily in he lysosomes . This led
o hei memb ane up u e a e ac i a ion o Pcs and induced apop osis wi h subsequen
seconda y nec osis. This ac was con i med by eal- ime moni o ing o Annexin V bind-
ing and he loss o cell memb ane in eg i y . In conclusion, his wo k has demons a ed
ha a bulky and igid a angemen o pe iphe al ca ionic subs i uen s is e y e icien o
p o iding good pho ophysical p ope ies and high pho odynamic ac i i y in he de elop-
men o no el pho osensi izes .
The s udy was suppo ed by he Czech Science Founda ion (P ojec No. 19-14758Y),
by he Cha les Uni e si y P ojec PRIMUS 20/SCI/013, by he G an Agency o Cha les
Uni e si y (P ojec No. 1620219) and om he p ojec o Speci ic Academic Resea ch
(SVV 260 550).
TOPOISOMERASE II INHIBITORS AND PREVENTION OF ANTRACYCLINE
TOXICITY ON CARDIOMYOCYTES
KUBEŠ, J .,1 JANSOVÁ, H .,1 KARABANOVICH, G .,2 MELNIKOVÁ, I .,2 JIRKOVSKÁ, A .,1
SKALICKÁ, V .,1 APPLOVÁ, L .,1 ROH, J .,2 ŠIMŮNEK, T.1
1 Depa men o Biochemical Sciences, Facul y o Pha macy in H adec K álo é, Cha les Uni e si y,
Czech Republic
2 Depa men o O ganic and Bioo ganic Chemis y, Facul y o Pha macy in H adec K álo é,
Cha les Uni e si y, Czech Republic
e-mail: kubesja1@ a .cuni .cz
An h acyclines (ANTs) emain indispensable in many cance ea men s . Use o all
d ugs o his class, howe e , is limi ed due o isk o se e e ca dio oxici y . To da e, dex a-
zoxane (ICRF-187) is s ill he only ca diop o ec i e agen app o ed o clinical use . This
compound, he e o e, ep esen s he main lead in he sea ch o e ec i e ca diop o ec i e
agen s . The ocus ega ding i s ca diop o ec i e mechanism has shi ed om me al chela-
ion o opoisome ase II (TOP2) modula ion, which is he aim o his wo k .
To gain mo e complex insigh in o he unde lying mechanism, di e se comme cially
a ailable compounds desc ibed in li e a u e as TOP2 inhibi o s we e sc eened on p ima y
cul u es o neona al a ca diomyocy es o abili y o p e en damage induced by dauno-
ubicin . Addi ionally, since he e a e no da a o he compounds being assessed o TOP2

81
inhibi ion side by side unde he same condi ions and owa d bo h TOP2 iso o ms, he
inhibi o s o in e es we e also assayed o hei espec i e inhibi o y po ency owa ds
bo h TOP2 iso o ms using deca ena ion assay . Since o he aim o his wo k is also a sea ch
o po en ial lead ca diop o ec i e agen (s), no el analogues o mos p omising inhibi o s
we e also s udied .
The combined esul s suppo he no ion ha TOP2 is in ol ed in he de elopmen o
ANT-induced ca dio oxici y bu he whole si ua ion appea s o be mo e complex as he e is
no a simple and di ec co ela ion be ween inhibi o y po ency and ca diop o ec ion . Mo e
de ailed in es iga ion o modes o TOP2 inhibi ion seems necessa y o p ope ly answe
his ques ion .
This s udy was suppo ed by he G an Agency o Cha les Uni e si y (P ojec No.
246219), InoMed (P ojec No. CZ.02.1.01/0.0/0.0/18_069/0010046) co- unded by he Eu-
opean Union and om he p ojec o Speci ic Academic Resea ch (SVV 260 550).
THE EFFECT OF SELECTIVE TOPOISOMERASE BETA INHIBITOR XK469
ON ANTHRACYCLINE CARDIOTOXICITY
SKALICKÁ, V., KUBEŠ, J., APPLOVÁ, L., JIRKOVSKÁ, A., ŠIMŮNEK, T.
Depa men o Biochemical Sciences, Facul y o Pha macy in H adec K álo é, Cha les Uni e si y,
wH adec K álo é, Czech Republic
e-mail: skalic 1@ a .cuni .cz
An h acycline (ANT) ca dio oxici y ep esen s a conside able limi a ion o se e al
an ineoplas ic egimes . As much as he ANT an icance e ec , hei ca dio oxici y e ec
excels in i s complexi y. Du ing hei long his o y, he scien i ic opinions shi ed om
he adi ionally discussed i on chela ion hypo hesis o opoisome ase II (TOP2) inhibi-
ion . TOP2 occu s in wo iso o ms wi h di e se unc ions . While TOP2 alpha (TOP2A)
is a c ucial enzyme o cell di ision and he eby is exp essed in eplica ing cells, TOP2
be a (TOP2B) is p esen in all cells including quiescen cells . Cu en ly, TOP2B has
been massi ely discussed as he po en ial mechanism o ANT ca dio oxici y . Al hough
dex azoxane (DEX) was app o ed by he FDA as a sa e and e icien ca diop o ec an ,
i s clinical use is limi ed only o speci ic g oups o pa ien s. One o he main easons o
he es ic ion is he conce n o he possible nega i e e ec on he an ineoplas ic ac i i-
y o ANT in he clinical se ing . This in e ac ion (al hough only specula i e) could be
based on he non-speci ic inhibi ion o bo h TOP2 iso o ms by DEX. The de elopmen
o TOP2B-speci ic inhibi o could p o ide a possible means o he e ec i e ca diop o-
ec ion a oiding he e ec on he cance cells . XK469 was desc ibed in li e a u e as
a TOP2B speci ic inhibi o ini ially disco e ed as an an ineoplas ic d ug ha p oceeded
o he second phase o se e al clinical ials . Ne e heless, i s use o ca diop o ec ion
has ne e been s udied . Ou pilo da a showed ha XK469 possesses an abili y o p e en
ca diomyocy es om ANT-induced cell dea h, al hough his e ec is complica ed wi h
he oxici y owa ds ca diomyocy es in highe doses and p olonged incuba ion imes . We
82
also desc ibed he XK469 inhibi o y ac i i y on indi idual TOP2 iso o ms . Mo eo e , i s
e ec s on ANT-induced apop osis and DNA damage we e de e mined by caspase assay,
come assay and assessmen o phospho yla ion o H2AX in bo h leukemic HL-60 cells
and ca diomyocy es .
The s udy was suppo ed by he Czech Science Founda ion (P ojec No. 18-08169S)
and om he p ojec o Speci ic Academic Resea ch (SVV 260 550).
TEPOTINIB REVERSES MULTIDRUG RESISTANCE BY INHIBITING
THE EFFLUX FUNCTION OF ABCB1 AND ABCG2 TRANSPORTERS IN VITRO
BUDAGAGA, Y .,1 VAGIANNIS, D .,1 ZHANG, Y .,1 SKARKA, A .,2 HOFMAN, J .1
1 Depa men o Pha macology and Toxicology, Facul y o Pha macy in H adec K alo é, Cha les Uni e si y,
Czech Republic
2 Facul y o Science, Uni e si y o H adec K álo é, H adec K álo é, Czech Republic
e-mail: budagagy@ a .cuni .cz
ABC (ATP-binding casse e) d ug e lux anspo e s play a c ucial pa in d ug-d ug
in e ac ions and mul id ug esis ance (MDR) o cance cells . Tepo inib, a no el c-MET y-
osine kinase inhibi o , has been ecen ly app o ed o he ea men o non-small cell lung
cance (NSCLC) . This s udy aims a he in es iga ion o he inhibi o y e ec o epo inib
on human ABC anspo e s and e alua ion o i s ole in MDR in i o . Fi s , esul s o
ou accumula ion expe imen s showed ha epo inib inhibi s ABCB1 and ABCG2 ans-
po e s . Second, using MTT assay we ound ha epo inib can e e se dauno ubicin and
mi oxan one esis ance media ed by ABCB1 and ABCG2, espec i ely . Fu he mo e, bi-
di ec ional anspo assays designa ed epo inib as ABCB1 subs a e wi h no a ini y o
ei he ABCC1 o ABCG2. In e es ingly, al hough ABCB1-media ed epo inib’s e lux was
demons a ed in anspo expe imen s, unc ional o e exp ession o ABCB1 in se e al
cellula models had no app eciable impac on i s an i umo ac i i y . Finally, epo inib did
no change he mRNA le els o ABCB1, ABCG2, and ABCC1 in selec ed cell lines by qRT-
PCR assay . To sum up, epo inib could pa icipa e in d ug-d ug in e ac ions by inhibi ing
he unc ion o ABCB1 and ABCG2 anspo e s and po en ially e e se he MDR in can-
ce cells . Ne e heless, ollow-up expe imen s wi h mo e sophis ica ed p eclinical models
a e necessa y o e i y possible clinical impac o ou esul s .
The s udy was suppo ed by he Czech Science Founda ion (P ojec No. 20-20414Y),
by he G an Agency o Cha les Uni e si y (p ojec No. 334120) and om he p ojec o
Speci ic Academic Resea ch (SVV 260 549).
83
THE ESTABLISHMENT OF EX VIVO PRIMARY LUNG TUMOR MODELS
AND THEIR APPLICATION FOR TESTING OF DRUG COMBINATIONS
VAGIANNIS, D .,1 MORELL, A .,2 ZHANG, Y .,1 BUDAGAGA, Y .,1 HANKE, I .,3 ROZKOŠ, T .,4
HOFMAN, J .1
1 Depa men o Pha macology and Toxicology, Facul y o Pha macy in H adec K álo é, Cha les Uni e si y,
Czech Republic
2 Depa men o Biochemical Sciences, Facul y o Pha macy in H adec K álo é, Cha les Uni e si y,
Czech Republic
3 Depa men o Ca diac Su ge y, Facul y o Medicine in H adec K álo é, Cha les Uni e si y
and Uni e si y Hospi al H adec K álo é, Czech Republic
4 Finge land Depa men o Pa hology, Facul y o Medicine in H adec K álo é, Cha les Uni e si y
and Uni e si y Hospi al H adec K álo é, Czech Republic
e-mail: agiannd@ a .cuni .cz
In his s udy, we aimed o es ablish ex i o explan s de i ed om non-small cell
lung cance (NSCLC) biopsies in coope a ion wi h clinicians . The NSCLC biopsies
om pa ien s we e ob ained immedia ely a e esec ion, which was ollowed by colla-
genase-assis ed libe a ion o umo cells om issues . NSCLC cells we e sepa a ed om
physiological cells and ib oblas s and he epi helial o igin o cells was con i med. Once
he p ima y cul u es we e es ablished, we de ec ed he p o ein exp ession le els o ABC
d ug e lux anspo e s (ABCB1, ABCG2, and ABCC1) in hem. Mo eo e , anspo e s’
unc ional ac i i y was assessed in he samples wi h de ec able exp ession by employing
he accumula ion low-cy ome ic s udies. In addi ion, in d ug combina ion s udies, we
demons a ed ha epo inib o e came anspo e -media ed esis ance o con en ional cy-
os a ics in p ima y explan s exhibi ing unc ional ac i i y . Finally, ABCB1, ABCG2 and
ABCC1 gene induc ion s udies showed ha epo inib does no ha e he po en ial o a ec
he mul id ug esis ance pheno ype o NSCLC cells . Ou esul s indica e ha epo inib
migh be a aluable candida e o he combina ion he apy o NSCLC umo s exp essing
d ug e lux anspo e s.
The s udy was suppo ed by he Czech Science Founda ion (P ojec No. 20-20414Y),
by he G an Agency o Cha les Uni e si y (P ojec No. 334120) and om he p ojec o
Speci ic Academic Resea ch (SVV 260 549).
The s udy was app o ed by he Uni e si y Hospi al E hics Commi ee (Documen
No. 202002 S04P).
SILENCING OF SELECTED UDP-GLYCOSYLTRANSFERASE GENES
BY RNAi IN HAEMONCHUS CONTORTUS
DIMUNOVÁ, D ., MATOUŠKOVÁ, P .
Depa men o Biochemical Sciences, Facul y o Pha macy in H adec K álo é, Cha les Uni e si y,
Czech Republic
e-mail: dimuno d@ a .cuni .cz
84
D ug esis ance is a se ious p oblem in many o ganisms, including pa asi es . The iden-
i ica ion o speci ic enzymes esponsible o d ug esis ance can lead o a new app oach o
he ea men . UDP-glycosyl ans e ases (UGTs), enzymes me abolizing xenobio ics and
eobio ics, p o ec he helmin h om he oxic ac ion o an helmin ics by hei con e sion
o inac i e glycosides .
In ou p ojec , we ocused on gas oin es inal nema ode, a pa asi e o small uminan s,
Haemonchus con o us, and e ela ion i s mechanism o d ug esis ance . RNA in e e -
ence (RNAi) was used o he cha ac e iza ion o gene unc ions in nema ode C. elegans .
The e o e we es ed he usabili y o his me hod in Haemonchus con o us . The silencing
o selec ed UGTs can p o e hei in ol emen in he me abolism o an helmin ics .
The silencing o selec ed UGTs can be media ed h ough speci ic double-s anded siR-
NA (small in e e ing RNA), which cause deg ada ion o he co esponding mRNA in i o
and lead o he selec ed enzymes loss o unc ion. The e icacy o gene supp ession by siR-
NA was op imized . Wo ms and la ae we e exposed o siRNA wi h di e en ans ec ion
eagen s by soaking and subsequen ly, he RNA was isola ed . The supp ession o es ed
genes was de e mined by qPCR analysis . Despi e all he e o s, ou selec ed enzymes we e
no possible o silence, he e o e ano he me hod o unc ional es ing has o be employed .
The s udy was suppo ed by he Czech Science Founda ion (P ojec No. 17-11954Y) and
om he p ojec o Speci ic Academic Resea ch (SVV 260 550).
USING MACHINE LEARNING IN EVALUATION OF IN VITRO VIABILITY TESTS
IN HAEMONCHUS CONTORTUS
NGUYEN, L. T., ŽOFKA, M., MAŠÁTOVÁ, E., SKÁLOVÁ, L.
Depa men o Biochemical Sciences, Facul y o Pha macy in H adec K álo é, Cha les Uni e si y,
Czech Republic
e-mail: nguyenli@ a .cuni .cz
Haemonchus con o us is a gas oin es inal pa asi e o sheep wi h g ea abili y o de-
elop esis ance o an helmin ic d ugs . Wi h he wo sening si ua ion, he e is a need o new
he apies, es ing o d ug sensi i i y as well as add essing he inc eases in nema ode esis -
ance . A p esen , he e a e se e al iabili y es s, each ha ing some limi a ions . Egg ha ch
es (EHT) and la al de elopmen es (LDT) a e commonly used in i o me hods which
a e ela i ely simple, ne e heless, hey equi e labo -in ensi e coun ing o eggs o la ae
a di e en s ages unde a mic oscope . In ou s udy, we applied machine lea ning in he
e alua ion pa o EHT and LDT, which was he objec de ec ion and classi ica ion om mi-
c oscopic images . We adop ed Mask Region-based Con olu ional Neu al Ne wo k (Mask
R-CNN)1 in Py hon 3, Ke as, and Tenso Flow model as i is he s a e-o - he-a app oach
o objec ecogni ion asks . We le e aged a p e-exis ing model and e- ained i using ou
da ase . By gene a ing bounding boxes and segmen a ion o each ins ance o an objec , he
model ecognizes eggs om i s -s age la ae and/o hi d-s age la ae. Using he Mask
R-CNN me hodology, we we e able o au oma e he p ocess o a high deg ee o accu acy .
85
The s udy was suppo ed by he Cha les Uni e si y P ojec UNCE 18/SCI/012 and om
he p ojec o Speci ic Academic Resea ch (SVV 260 550).
Re e ences
1. HE, K ., GKIOXARI, G ., DOLLÁR, P . e al.: Mask R-CCN . In P oceedings o 2017 IEEE In e na ional
Con e ence on Compu e Vision (ICCV), Venice, I aly, 22–29 Oc . 2017, pp . 2980–2988 .
SERTRALINE AS A NEW POTENTIAL ANTHELMINTICS
AGAINST HAEMONCHUS CONTORTUS?
ZAJÍČKOVÁ, M.,1 NAVRÁTILOVÁ, M .,1 PRCHAL, L .,2 NGUYEN, L . T .,1 STUCHLÍKOVÁ, R. L.,1
SKÁLOVÁ L .1
1 Depa men o Biochemical Sciences, Facul y o Pha macy in H adec K álo é, Cha les Uni e si y,
Czech Republic
2 Biomedical Resea ch Cen e, Uni e si y Hospi al H adec K álo é, Czech Republic
e-mail: zajickm@ a .cuni .cz
Haemonchus con o us is a pa asi ic nema ode o small uminan s which cause p oblem
o many a me s a ound he wo ld . G azing managemen , biological con ol o pas u es,
nu i ional suplemen a ion, accina ion and selec i e b eading play impo an ole in
p e en ion o his disease . Howe e , chemo e apy s ill ep esen s he main s a egy o
con ol in ec ions caused by H. con o us . Due o wide sp ead esis ance o main clases o
an helmin ics (benzimidazoles, mac ocyclic lac ones, amino-ace oni ile de i a i e) i is
necessa y o look o new s uc u es . Syn hesis o new chemical en i ies is complica ed,
long, and cos ly p ocess. Fo his eason, exploi ing old s uc u es and inding new in-
dica ions o al eady egis e ed d ugs ep esen a good al e na i e .1 Se aline is used in
human medicine as an idep esan and belongs o he class o selec i e se o onin eup ake
inhibi o s . Se aline showed o be e ec i e agains T ichu is mu is, Ancylos oma caninum
and Schis osoma mansoni .2 In ou p ojec we wan ed o know i se aline is also e ec i e
agains H. con o us . Mo eo e , we a e in e es ed abou i s bio ans o ma ion and hepa o-
oxici y in he hos sheep .
The s udy was suppo ed by he Cha les Uni e si y G an Agency (P ojec No. 1568519)
and om he p ojec o Speci ic Academic Resea ch (SVV 260 550).
Re e ences
1. ZAJÍČKOVÁ, M., NGUYEN, L. T., SKÁLOVÁ, L. e al .: D ug Disco . Today, 25, 2020, 430–437 .
2. WEEKS, J . C ., ROBERTS, W . M ., LEASURE, C . e al .: Sci . Rep ., 8, 2018, a . 975 .

86
METABOLISM OF HELENALIN IN VITRO AND ITS INTERACTION
WITH HUMAN CYTOCHROME P450 2A13
ŠADIBOLOVÁ, M .,1 BOUŠOVÁ, I .,1 JUVONEN, R .,2 AURIOLA, S .2
1 Depa men o Biochemical Sciences, Facul y o Pha macy in H adec K álo é, Cha les Uni e si y,
Czech Republic
2 School o Pha macy, Facul y o Heal h Sciences, Uni e si y o Eas e n Finland, Kuopio, Finland
e-mail: sadibolm@ a .cuni .cz
Helenalin (HEL) is a sesqui e pene lac one, especially ound in A nica mon ana and A -
nica chamissonis, ha demons a es po en an i-in lamma o y ac i i y media ed by di ec
alkyla ion o Cys38 wi hin he DNA binding domain o RelA (p65), a key membe o he
nuclea ac o -κB (NF-κB) amily o ansc ip ion ac o s. Besides, HEL has been ound
o exe ema kable an icance , an ibac e ial and an ip o ozoal ac i i y . HEL is an ac i e
componen o he bal a nica p epa a ions ha ha e long been used o educe muscle and
join pain, pos -su gical pain as well as o ea mino spo s inju ies, b uises and swelling
associa ed wi h auma, con usions and sp ains . Despi e he equen use o hese p oduc s,
nei he he a e o HEL in he human o ganism, no i s in e ac ion wi h xenobio ic-me abo-
lizing enzymes has been s udied so a . To add ess his issue, we ha e i s in es iga ed he
me abolism o HEL and cha ac e ized he kine ics o me aboli e o ma ion using human
and a li e subcellula ac ions and human ecombinan cy och ome P450 (CYP) en-
zymes. UHPLC-MS/MS echnique was employed o his pu pose. HEL was oxidized in o
i e me aboli es by bo h human and a li e mic osomes, and he oxida ion was gene ally
a mo e e icien in a mic osomes. Mo eo e , se e al human CYP iso o ms we e ound
o be in ol ed in he oxida ion o HEL, namely CYP2A13, 2B6, 3A4, 3A5 and 3A7 . In
he ollowing expe imen s, we ha e also es ed he inhibi o y po en ial o HEL owa ds hu-
man ecombinan CYP enzymes . Ou o all es ed CYPs, he mos e ec i e inhibi ion ( he
lowes IC50 alue) was obse ed o CYP2A13 . In addi ion, he inhibi ion o CYP2A13
was NADPH- and ime-dependen sugges ing ha HEL may ac as a mechanism-based
inhibi o o CYP2A13 .
The s udy was suppo ed by he Czech Science Founda ion (P ojec No. 18-09946S), by
he Cha les Uni e si y G an Agency (P ojec No. 302120) and om he p ojec o Speci ic
Academic Resea ch (SVV 260 550).
UDP-GLYCOSYLTRANSFERASES AND ALBENDAZOLE METABOLISM
IN THE JUVENILE STAGES OF HAEMONCHUS CONTORTUS
KELLEROVÁ, P ., NAVRÁTILOVÁ, M ., NGUYEN, L . T ., DIMUNOVÁ, D .,
RAISOVÁ STUCHLÍKOVÁ, L., ŠTĚRBOVÁ, K., SKÁLOVÁ, L., MATOUŠKOVÁ, P.
Depa men o Biochemical Sciences, Facul y o Pha macy in H adec K álo é, Cha les Uni e si y,
Czech Republic
e-mail: obo ilp@ a .cuni .cz
87
The UDP-glycosyl ans e ases (UGTs), second phase bio ans o ma ion enzymes,
inac i a e xenobio ic subs a es . Such ans o ma ion is in ol ed in d ug- esis ance mecha-
nisms in one o he mos pa hogenic pa asi es in small uminan s, Haemonchus con o us .
In he p e ious s udy, we cha ac e ized he UGT amily in H. con o us, including i s
nomencla u e, phylogeny, and exp ession in adul s – he pa asi ic li e s age .1 Howe e ,
he d ug-me abolism by UGTs in he ee-li ing ju enile s ages may as well ep esen an
impo an de ence sys em agains an helmin ics . Due o he almos pe manen con ac wi h
an helmin ic esidues exc e ed om ea ed animals in he en i onmen ,2 UGTs in ju enile
s ages may also con ibu e o d ug- esis ance de elopmen . The e o e, we decided o s udy
he exp ession o UGTs and he me abolism o albendazole (ABZ) and he p ima y ac i e
ABZ me aboli e ABZ sul oxide (ABZSO) in he eggs, L1s, and L3s la ae o H. con o us .
We ha e also compa ed he o ma ion o ABZ me aboli es and selec ed UGT ansc ip s
be ween a sensi i e isola e (ISE) and esis an isola es (IRE and mul i- esis an WR) . Fu -
he mo e, we explo ed he inducibili y o UGTs by ABZ and ABZSO in H. con o us
ju enile s ages .3
The s udy was suppo ed by he Czech Science Founda ion (P ojec No. 17-11954Y), by
he Cha les Uni e si y p ojec s (PRIMUS/17/SCI/4 and UNCE/18/SCI/012) and om he
p ojec o Speci ic Academic Resea ch (SVV 260 550).
Re e ences
1. MATOUŠKOVÁ, P ., LECOVÁ, L ., LAING, R . e al .: In . J . Pa asi ol ., 8, 2018, 420–429 .
2. PRCHAL, L ., PODLIPNÁ, R ., LAMKA, J . e al .: En i on . Sci . Pollu . Res ., 23, 2016, 13015–13022 .
3. KELLEROVÁ, P ., NAVRÁTILOVÁ, M ., NGUYEN, L . T . e al .: F on . Physiol ., 11, 2020, a . 594116 .
TESTING FERN EXTRACTS FRACTIONS ON ANTI-INFLAMMATORY
AND ANTHELMINTIC PROPERTIES
PAVIČIĆ, A.,1,2 SZOTÁKOVÁ, B .,1 LANGHANSOVÁ, L .2
1 Depa men o Biochemical Sciences, Facul y o Pha macy in H adec K álo é, Cha les Uni e si y,
Czech Republic
2 Ins i u e o Expe imen al Bo any, Czech Academy o Sciences, P ague, Czech Republic
e-mail: pa icia@ a .cuni .cz
Fe ns a e used in adi ional medicine in Asia and he apeu ic e ec s o se e al e n
ex ac s ha e been p o en . Howe e , he e is s ill space o sea ching o new bioac i e
phy ochemicals in e ns. P e ious esul s showed signi ican an i-in lamma o y ac i i y
o se e al selec ed e n species wi h highe po en ial in selec i e COX-1 inhibi ion com-
pa ing o mode a e inhibi ion o COX-2 and 5-LOX ac i i y . Based on hese esul s we
decided o make ac iona ion o ex ac s o h ee e n species (A hy ium dis en i olium,
D yop e is aemula and Blechnum spican ) by using sequen ial liquid-liquid echniques .1
Redissol ed ac ions (n-hexane, chlo o o m, e hylace a e, n-bu anol) and esidual aque-
ous ac ion ha e been es ed o an i-in lamma o y and an helmin ic ac i i y. D yop e is
aemula showed he highes po en ial o all ac ions in selec i e COX-1 inhibi ion, i s
88
n-hexane and chlo o o m ac ions showed only mode a e selec i e COX-2 and 5-LOX
inhibi ion . All e n species and hei ac iona ed ex ac s ha e been es ed o an helmin ic
ac i i y using Egg Ha ch Tes 2 wi h Ba be ’s pole wo ms (Haemonchus con o us) . None
o he e n samples educed egg ha ching in EHT compa ed wi h he con ol .
The s udy was suppo ed om he p ojec o Speci ic Academic Resea ch (SVV 260 550).
Re e ences
1. LANGHANSOVÁ, L ., LANDA, P ., KUTIL, Z . e al.: Food Ag ic . Immunol ., 28, 2017, 343–353 .
2. Von SAMSON-HIMMELSTJERNA, G ., COLES, G . C ., JACKSON, F . e al .: Pa asi ol . Res ., 105, 2009,
825-834 .
IN VITRO EVALUATION OF THE PHOTODYNAMIC ACTIVITY OF NOVEL
BODIPY DYES
ROHLÍČKOVÁ, M.,1 KRZEMIEN, W .,2 ZIMČÍK, P.,2 MACHÁČEK, M.1
1 Depa men o Biochemical Sciences, Facul y o Pha macy in H adec K álo é, Cha les Uni e si y,
Czech Republic
2 Depa men o Pha maceu ical Chemis y and Pha maceu ical Analysis, Facul y o Pha macy
in H adec K álo é, Cha les Uni e si y, Czech Republic
e-mail: s eklam@ a .cuni .cz
Neoplas ic diseases a e nowadays one o he mos common easons o dea h in de-
eloped coun ies . The e o e, a g ea a en ion is dedica ed o he de elopmen o new
me hods o he ea men o hose diseases . One o such me hods is he pho odynamic
he apy (PDT) . This is a selec i e, minimally in asi e me hod wi h a minimum side e -
ec s . P inciple o PDT is he applica ion o inac i e d ug, called pho osensi ize (PS),
ollowed by exposu e o ac i a ing ligh wi h sui able wa eleng h in he p esence o mo-
lecula oxygen . The e o e, he pho odynamic he apy needs h ee basic componen s: he
PS, ligh and oxygen .1,2
As i has been said, one o he mos impo an pa o PDT is he PS . The objec i e o
his s udy is assessing he e ec i eness o he no el PSs om he g oup o BODIPY dyes
in i o . All o he s udied compounds we e e alua ed on malignan human ce ical cell
line (HeLa) and human melanoma cell line SK-MEL-28 . Cy o oxici y a e he exposu e
o ac i a ing ligh (pho o oxici y) and in insic oxici y in he absence o ligh (da k oxic-
i y) we e de e mined . Fu he , he subcellula localiza ion PSs a e accumula ion in cells
was assessed using con ocal mic oscopy and luo escen o ganelle-speci ic p obes. All o
s udied compounds p o ed o be e icien PSs (EC50 up o 0.14 ± 0.01 μM) wi h no da k
oxici y up o hei solubili y limi .
The s udy was suppo ed om he p ojec o Speci ic Academic Resea ch (SVV 260 550).
89
Re e ences
1. AGOSTINIS, P ., BERG, K ., CENGEL, K . A . e al .: CA Cance J . Clin ., 61, 2011, 250–281 .
2. KAMKAEW, A ., LIM, S . H ., LEE, H . B . e al .: Chem . Soc . Re ., 42, 2013, 77–88 .
CAROTUXIMAB AFFECTS ENDOGLIN EXPRESSION AND ADHESION
AND TRANSMIGRATION OF MONOCYTES VIA ENDOTHELIAL CELLS
IN 7-KETOCHOLESTEROL INDUCED ENDOTHELIAL DYSFUNCTION
TRIPSKÁ, K .,1 VICEN, M .,1 HAVELEK, R .,2 IGREJA E SÁ, I . C .,1 EISSAZADEH, S .,1 VITVEROVÁ, B .,1
NACHTIGAL, P .1
1 Depa men o Biological and Medical Sciences, Facul y o Pha macy in H adec K álo é, Cha les Uni e si y,
Czech Republic
2 Depa men o Medical Biochemis y, Facul y o Medicine in H adec K álo é, Cha les Uni e si y,
Czech Republic
e-mail: ipskak@ a .cuni .cz
Endoglin (Eng) is a ansmemb ane glycop o ein a ec ing TGF-β signaling pa hway.
In he p e ious s udy, we demons a ed ha ea men o endo helial cells wi h 7-ke ocho-
les e ol (simula ing oxidized LDL) leads o he de elopmen o endo helial dys unc ion
wi h up egula ed le els o Eng, cell adhesion molecules (ICAM-1, P/E-selec in), and also
inc eased adhesion and ansmig a ion o monocy es ia endo helial cells . Ca o uximab
(TRC105) is a no el monoclonal an ibody ha binds Eng wi h high a ini y and block/
inhibi s i s e ec s, cu en ly s udied in di e en clinical ials mos ly ocused on cance .
We hypo hesized ha ca o uximab media ed inhibi ion o endoglin will a ec 7-ke ocho-
les e ol induced endo helial dys unc ion . Human ao ic endo helial cells (HAEC), passage
5, we e cul u ed wi h app op ia e supplemen s un il eaching 90% con luence. A e wa ds,
cells we e ea ed wi h o wi hou 300 μg mL‒1 ca o uximab o 1 hou ollowed by ad-
di ion o 10 µg mL‒1 7-ke ocholes e ol o ano he 12 hou s . Gene exp ession o Eng,
cell adhesion molecules and Eng ansc ip ion ac o s (KLF6, NF-kB p65 and LXR) was
measu ed by qRT-PCR . P o ein le els o Eng, adhesion molecules, MMP-14, pSmads and
adhesion assay we e quan i ied by low cy ome y. Soluble endoglin le els we e measu ed
by ELISA . T ansmig a ion assay was pe o med wi h cell cul u e inse s and assessed by
low cy ome y. We demons a ed ha ca o uximab was able o p e en 7-ke ocholes e ol
induced Eng and ICAM-1 exp ession, as wells as adhesion and ansmig a ion o mono-
cy es ia endo helial cells . The e o e, we p opose ha ca o uximab migh be impo an
in p e en ion o endo helial dys unc ion induced by hype choles e olemia, bu o which
ex en mus be u he in es iga ed .
This s udy was suppo ed by he G an Agency o Cha les Uni e si y (P ojec
No. 1130120) and om he p ojec o Speci ic Academic Resea ch (SVV 260 549).
96
conduc ed in acu e and communi y ca e (71 .1 and 53 .8% s 34 .5 and 31 .5%, espec i e-
ly). This e iew con i med ha PIP is highly p e alen in he CEE egion, u he mo e,
hese esul s will se e as a s a ing poin o ou scien i ic wo ks on analyses o PIP
p e alence in se e al EU and non-EU coun ies pa icipa ing in he ESR7 Eu oAgeism
H2020 p ojec .
The s udy was suppo ed by he Eu oAgeism Eu opean Union’s Ho izon 2020 e-
sea ch and inno a ion p og amme unde he Ma ie Skłodowska-Cu ie g an ag eemen
No. 764632, by InoMed (P ojec No. CZ.02.1.01/0.0/0.0/18_069/0010046) co- unded by
he Eu opean Union, by he Resea ch p og amme De elopmen and S udy o D ugs (P o-
g es Q42) and om he p ojec o Speci ic Academic Resea ch (SVV 260 551).
Re e ences
1. RANKIN, A ., CADOGAN, C ., PATTERSON, S . e al .: Coch ane Da abase Sys . Re ., 9, 2018, a . CD008165 .
2. ALLDRED, D ., KENNEDY, M ., HUGHES, C . e al .: Coch ane Da abase Sys . Re ., 2, 2016, CD009095 .
3. FIALOVÁ, D ., TOPINKOVÁ, E ., GAMBASSI, G . e al.: JAMA, 293, 2005, 1348‒1358.
4. GALLAGHER, P ., LANG, P ., CHERUBINI, A . e al.: Eu . J. Clin. Pha macol., 67, 2011, 1175‒1188.
PRESCRIBING OF HYPNOSEDATIVES IN SENIORS IN ACUTE
AND AMBULATORY CARE IN THE CZECH REPUBLIC – INOMED
AND EUROAGEISM H2020 PROJECT FINDINGS
ANTONENKO, O .,1 PULDOVÁ, K .,1 ZELINKOVÁ, A .,1 HALAČOVÁ, M.,1,2 GREŠÁKOVÁ, S .,1
BRKIĆ, J.1, FIALOVÁ, D .1,3
1 Depa men o Social and Clinical Pha macy, Facul y o Pha macy in H adec K álo é, Cha les Uni e si y,
Czech Republic
2 Depa men o Clinical Pha macy, Hospi al Na Homolce, P ague, Czech Republic
3 Depa men o Ge ia ics and Ge on ology, 1s Facul y o Medicine and Gene al Uni e si y Hospi al
in P ague, Cha les Uni e si y, Czech Republic
e-mail: an onenol@ a .cuni .cz
Insomnia is a equen p oblem in olde adul s, pa icula ly in hose su e ing om
polymo bidi y and ea ed by polypha macy . The aim o ou s udy was o desc ibe he
p e alence o insomnia and pa e ns o po en ially inapp op ia e p esc ibing in hypnoseda-
i e d ug use in acu ely hospi alized and ambula o y ca e senio s in he Czech Republic .
E alua ed da a comp ised comp ehensi e ge ia ic cha ac e is ics (CGC) o 438 acu ely
hospi alized and 563 ambula o y ca e ge ia ic pa ien s (≥ 65 yea s) om egionally di -
e en s udy si es in he Czech Republic (P ague, B no, H adec K álo é) . All pa ien s we e
p ospec i ely assessed using he Eu oAgeism H2020 s udy p o ocols . Desc ip i e s a is ics
was applied in da a analysis . On he whole, 34 .6% (n = 151) o acu ely hospi alized senio s
and 30 .6% (n = 172) in ambula o y ca e had eco ded diagnosis o insomnia in pe sonal
his o y, espec i ely. The mos equen ly used hypnoseda i es we e: an ipsycho ics e/n
(18 .5% and 17 .8%), Z-d ugs (16 .2% and 8 .2%) and benzodiazepines (14 .2% and 7 .6%) .
We de e mined also non-ge ia ic dosing o Z-d ugs (10 .5% and 6,0%, espec i ely) and
BZDs (0 .5% and 2 .7%), as well as non-ge ia ic lengh o d ug he apy o Z-d ugs (5 .9%

97
and 2 .7%, espec i ely) and BZDs (5 .3% and 11%, espec i ely) . Excessi e indica ion
o an ipsycho ics e/n and inapp op ia e ge ia ic dosing o Z-d ugs and long- e m use o
BZDs e/n we e documen ed in senio s in he Czech Republic.
The s udy was suppo ed by InoMed (P ojec No. CZ.02.1.01/0.0/0.0/18_069/0010046)
co- unded by he Eu opean Union, by he Eu oAgeism Eu opean Union’s Ho izon 2020
esea ch and inno a ion p og amme unde he Ma ie Skłodowska-Cu ie g an ag eemen
No. 764632, by he Resea ch p og amme De elopmen and S udy o D ugs (P og es Q42)
and om he p ojec o Speci ic Academic Resea ch (SVV 260 551).
AGEING IN DEVELOPING COUNTRIES AND PHYSICIAN’S KNOWLEDGE
OF EXPLICIT CRITERIA OF PIMs IN OLDER PATIENTS AND BARRIERS
TOWARDS APPROPRIATE GERIATRIC PRESCRIBING
BANDARI, D . K .,1 BRKIĆ, J.,1 FIALOVA, D .1,2
1 Depa men o Social and Clinical Pha macy, Facul y o Pha macy in H adec K alo é, Cha les Uni e si y,
Czech Republic .
2 Depa men o Ge ia ics and Ge on ology, 1s Facul y o Medicine in P ague, Cha les Uni e si y,
Czech Republic .
e-mail: laxmideepak .pha ma@gmail .com
Po en ially Inapp op ia e Medica ion (PIM) use is associa ed wi h inc eased mo al-
i y and mo bidi y in olde adul s and p esc ibing pa e ns a e s ongly in luenced by
physicians’ knowledge o ge ia ic p esc ibing . We aimed o assess he ba ie s among
physicians o app op ia e ge ia ic p esc ibing, hei knowledge o speci ic explici c i-
e ia o PIMs and he equency o use o di e en in o ma ion sou ces and guidelines .
A desc ip i e pilo c oss-sec ional s udy was conduc ed among physicians (n = 256) in
wo e ia y ca e eaching hospi als . Knowledge and p e e ences in usage o di e en
in o ma ion sou ces and ba ie s o app op ia e ge ia ic p esc ibing we e assessed by
alida ed clinical igne es and by a pilo ed ques ionnai e . Pea son’s chi-squa ed es ,
S uden ’s - es , Mann–Whi ney’s U es and logis ic eg ession models we e applied
using s a is ical R so wa e ( e sion 4 .0 .3) . O 201 (78 .5%) esponden s, majo i y we e
males (63 .2%), 74 .1% ecei ed aining in ge ia ic medicine and 39 .8% we e cu en ly
p o iding mo e han once a week ca e o olde adul s in long- e m ca e acili ies . Only
31.8% o physicians el con iden in app op ia e ge ia ic p esc ibing and mean sco e o
knowledge o PIMs by clinical igne es was 3 .5 ± 0 .9 . Mul i a ia e logis ic eg ession
e ealed he highe odds o good ge ia ic knowledge in emales, age g oup o 30–39
yea s, and in physicians ha ecei ed ge ia ic aining . Posi i e end o be e sco ing
in clinical igne es co ela ed wi h he ex end o use o PIM c i e ia . Limi ed op ions in
d ug o mula ies (80 .6%), lack o accep able he apeu ic al e na i es (69 .1%), po en ial
d ug-d ug in e ac ions (63 .6%) and lack o ime (62 .1%) we e he op ci ed ba ie s o
app op ia e p esc ibing in olde adul s . Educa ional in e en ions and in e p o essional
clinical pha macy coope a ion may imp o e app op ia eness o ge ia ic p esc ibing in
daily clinical p ac ice .
98
The s udy was suppo ed by he Eu oAgeism Eu opean Union’s Ho izon 2020 e-
sea ch and inno a ion p og amme unde he Ma ie Skłodowska-Cu ie g an ag eemen
No. 764632, by InoMed (P ojec No. CZ.02.1.01/0.0/0.0/18_069/0010046) co- unded by
he Eu opean Union, by he Resea ch p og amme De elopmen and S udy o D ugs (P o-
g es Q42) and om he p ojec o Speci ic Academic Resea ch (SVV 260 551).
PREVALENCE OF POLYPHARMACY AND RISKS OF POTENTIALLY
INAPPROPRIATE MEDICATION USE IN OLDER POPULATION
IN A DEVELOPING COUNTRY: A SYSTEMATIC LITERATURE REVIEW
AND META-ANALYSIS
BHAGAVATHULA, A . S .,1 FIALOVÁ, D .1,2
1 Depa men o Social and Clinical Pha macy, Facul y o Pha macy in H adec K álo é, Cha les Uni e si y,
Czech Republic .
2 Depa men o Ge ia ics and Ge on ology, 1s Facul y o Medicine in P ague, Cha les Uni e si y,
Czech Republic
e-mail: bhaga aa@ a .cuni .cz
Aim: This sys ema ic li e a u e e iew and me a-analysis aimed o in es iga e he
p e alence o polypha macy and PIM use and majo isk ac o s associa ed wi h PIM
p esc ibing in olde adul s in E hiopia .
Me hods: We sea ched PubMed/MEDLINE, Scopus, Embase, and Google Schola
da abases o iden i y ele an s udies published be ween Janua y 1990 o Oc obe 2020 .
Obse a ional s udies epo ing he p e alence and associa ion o isk ac o s wi h polyp-
ha macy and PIM use in olde popula ion we e me a-analyzed . A mul ile el me a-analysis
was conduc ed o pool he p e alence es ima es, and he isk o PIM use was epo ed as
a ela i e isk (RR) wi h 95% con idence in e al (CI).
Resul s: We iden i ied by sys ema ic li e a u e e iew 404 a icles. O hose, eigh
s udies ul illed inclusion c i e ia, comp ising a o al sample o 2608 pa icipan s. The
o e all p e alence o polypha macy and PIM use pooled by me a-analysis in he E hio-
pian olde popula ion was 33% and 37%, espec i ely . The isk ac o s o PIM use we e
analyzed in he me a-analysis (pa icula ly polymo bidi y, polypha macy, gende , and
olde age), he olde age o 65+ (RR:1.71, 95% CI: 1.16–2.51) was signi ican ly associ-
a ed wi h PIM use .
Conclusion: This i s me a-analysis om a de eloping coun y e ealed a high p e -
alence o polypha macy and PIM use in he E hiopian olde popula ion . The e was no
awa eness o he isk o PIMs in pa ien s wi h polypha macy and polymo bidi y, and only
olde age signi ican ly p edic ed PIM use. In e en ions ensu ing a ional ge ia ic pha -
maco he apy a e essen ial no only in de eloped coun ies, bu also in de eloping coun ies
in o de o educe he expec ed bu den o PIM- ela ed ge ia ic mo bidi y, highe cos s,
and mo ali y .
The s udy was suppo ed by InoMed (P ojec No. CZ.02.1.01/0.0/0.0/18_069/0010046)
co- unded by he Eu opean Union, by he Eu oAgeism Eu opean Union’s Ho izon 2020
99
esea ch and inno a ion p og amme unde he Ma ie Skłodowska-Cu ie g an ag eemen
No. 764632, by he Resea ch p og amme De elopmen and S udy o D ugs (P og es Q42)
and om he p ojec o Speci ic Academic Resea ch (SVV 260 551).
RISK STRATIFICATION OF PATIENTS FOR POSTOPERATIVE INFECTION
AFTER KNEE OR HIP ARTHROPLASTY – PRELIMINARY RESULTS
DOMECKÝ, P .,1 REJMAN PATKOVÁ, A .,1 KUČERA, T.,2 ŠPONER P .,2 MALÝ, J .1
1 Depa men o Social and Clinical Pha macy, Facul y o Pha macy in H adec K álo é, Cha les Uni e si y,
Czech Republic
2 Depa men o O hopedics, Uni e si y Hospi al H adec K álo é, Czech Republic
e-mail: domeckyp@ a .cuni .cz
Su gical si e in ec ion is a po en ial complica ion o all su gical p ocedu es . The e is
double mo ali y in pa ien s wi h de eloped in ec ion who unde wen a su gical p ocedu e
compa ed o non-in ec ed pa ien s . This s udy aimed o s a i y pa ien s acco ding o he
isk o pos ope a i e in ec ion and e i y he indings in clinical p ac ice. This p ospec i e
s udy has s a ed in Ma ch 2020 in he Depa men o O hopedics a Uni e si y Hospi al
H adec K álo é. The s udy included pa ien s aged ≥ 18 yea s who unde wen hip o knee
a h oplas y. In lamma o y ma ke s, especially neu ophil- o-lymphocy e a io (NLR),
p ognos ic in lamma o y and nu i ional index (PINI) and in ensi e ca e in ec ion sco e
(ICIS), we e analyzed one day be o e ope a ion (−1D), wo days a e ope a ion (2D) and
in ou pa ien examina ion (OE) . 42 pa ien s (16 women and 26 men) wi h an a e age age o
64 .04 ± 10 .21 we e included in he s udy . Hip a h oplas y unde wen 31 (73 .8%) and knee
a h oplas y 11 (26 .2%) pa ien s . Ce azolin was adminis e ed in 88 .1% and ancomycin
in 11 .9% o ope a ions .
−1D: NLR > 4, PINI sco e > 21 and ICIS > 4 we e iden i ied in 5, 0, and 1 pa ien ,
espec i ely. 2D: NLR > 4, PINI sco e > 21 and ICIS > 4 we e iden i ied in 14, 24, and
4 pa ien s, espec i ely. OE: NLR > 4, PINI sco e > 21 and ICIS > 4 we e iden i ied in no
pa ien a all. ACS (Ame ican Socie y o Su geons) isk sco e > 5% was iden i ied in 9 pa-
ien s. The pos ope a i e in ec ion was iden i ied in 2 (4.7%) pa ien s and pos ope a i e
anemia in 12 (28 .6%) pa ien s . The a e age leng h o hospi aliza ion was 11 ± 6 .7 days .
Inc eased in lamma o y ma ke s could be sui able o de ec ing ea ly pos ope a i e in ec-
ion . Howe e , a mo e ex ensi e se o pa ien s is needed o u he de ailed s a is ical
analysis .
The s udy was suppo ed by he p ojec o Speci ic Academic Resea ch (SVV 260 551).
100
PREVALENCE AND RISK FACTORS OF CARDIOVASCULAR DRUG – DISEASE
INTERACTIONS IN SENIORS IN ACUTE AND AMBULATORY CARE
IN THE EUROAGEISM H2020 PROJECT
KUMMER, I .,1 BRKIĆ, J.1 LUKAČIŠINOVÁ, A.,1 REISSIGOVÁ, J .,2 FIALOVÁ, D .1
1 Depa men o Social and Clinical Pha macy, Facul y o Pha macy in H adec K álo é, Cha les Uni e si y,
Czech Republic
2 Depa men o S a is ical Modeling, Ins i u e o Compu e Sciences o he Czech Academy o Sciences,
P ague, Czech Republic
e-mail: ing id .kumme 2@gmail .com
Olde pa ien s a e ulne able o d ug-disease in e ac ions (DDIs) because o age- ela ed
pha macological changes, polymo bidi y, and polypha macy . The aim o his s udy was o
in es iga e he p e alence and isk ac o s o ca dio ascula (CVS) DDIs in olde adul s in
ambula o y and acu e ca e acili ies in he Czech Republic . The da a p esen ed a e p elimi-
na y. Da a o 1152 pa ien s 65+ we e collec ed using he Eu oAgeism H2020 p o ocols in
4 acu e ca e hospi als and 4 ambulances (Jun 2019 – Jan 2020) . P e alence and isk ac o s
o CVS DDIs we e iden i ied acco ding o STOPP/START c i e ia, he EU(7) PIM lis and
Bee s 2019 c i e ia. The majo i y o pa icipan s we e emales (67.4%) and 38.7% we e 85+
yea s old. Polypha macy (5+ medicines) was iden i ied in 85.3% pa ien s and 90.0% su e ed
om polymo bidi y (4+ diagnoses). P e alence o a leas 1 CVS DDIs was: by START c i-
e ia 75 .4%, STOPP c i e ia 30 .7%, EU(7) PIM c i e ia 29 .0% and BEERS c i e ia 21 .9% .
Highe odds o being p esc ibed a leas 1 CVS DDIs we e in senio s su e ing om 2+ CVS
diagnoses (OR = 12 .2, 95% CI 7 .3–21 .5, p < 0 .001), in polypha macy use s (OR = 2 .2, 95%
CI 1.3–3.9, p = 0.005), and in 85+ yea s old senio s (OR = 3.1, 95% CI 1.6–6.1, p = 0.001).
Ou s udy documen ed high p e alence o CVS DDIs and isk ac o s in olde pa ien s in
di e en ca e se ings in he Czech Republic . The e o e, sa e ge ia ic p esc ibing should be
p omo ed, and egula medica ion check p o ided by clinical pha macis s .
The s udy was suppo ed by he Eu oAgeism Eu opean Union’s Ho izon 2020 e-
sea ch and inno a ion p og amme unde he Ma ie Skłodowska-Cu ie g an ag eemen
No. 764632, by InoMed (P ojec No. CZ.02.1.01/0.0/0.0/18_069/0010046) co- unded by
he Eu opean Union, by he Resea ch p og amme De elopmen and S udy o D ugs (P o-
g es Q42) and om he p ojec o Speci ic Academic Resea ch (SVV 260 551).
DRUG-RELATED HOSPITAL ADMISSIONS VIA THE EMERGENCY
DEPARTMENT: A CROSS-SECTIONAL STUDY
OČOVSKÁ, Z.,1 MAŘÍKOVÁ, M.,1,2 KOČÍ, J.,3 VLČEK, J.1,2
1 Depa men o Social and Clinical Pha macy, Facul y o Pha macy in H adec K álo é, Cha les Uni e si y,
Czech Republic
2 Depa men o Clinical Pha macy, Hospi al Pha macy, Uni e si y Hospi al H adec K álo é, Czech Republic
3 Depa men o Eme gency Medicine, Uni e si y Hospi al H adec K álo é, Czech Republic
e-mail: oco skaz@ a .cuni .cz
101
D ug- ela ed hospi al admissions (DRA) ha e a ac ed much esea ch a en ion wo ld-
wide . The aims o his s udy we e o de e mine he p e alence and p e en abili y o DRA,
o iden i y he implica ed medica ions in DRA and o examine he p e en abili y aspec s
o DRA . The s udy examined hospi al admissions ia he eme gency depa men in he
Uni e si y Hospi al H adec K álo é be ween Augus and Sep embe 2018 . Planned hos-
pi alisa ions and isi s o he eme gency oom wi hou inpa ien hospi alisa ion we e no
included . The da a we e collec ed e ospec i ely using elec onic medical eco ds . The
p ocess o DRA iden i ica ion included sc eening o po en ial ad e se d ug e en s which
we e he main o con ibu o y eason o hospi al admissions, causali y assessmen and
assessmen o con ibu ion o hospi al admission . DRA due o medica ion e o s we e
conside ed p e en able and DRA due o ad e se d ug eac ions we e conside ed non-
p e en able. Ana omical The apeu ic Chemical classi ica ion sys em was used o he
classi ica ion o medica ions implica ed in DRA. Ou o 1204 hospi al admissions 193 ha e
been iden i ied as DRA. 144 DRA we e ela ed o ea men sa e y while 49 DRA we e
ela ed o ea men e ec i eness . The p e alence o DRA was 16 .0% (95% CI 14 .0–18 .1)
and he p e en abili y o DRA was 54 .4% (95% CI 47 .4–61 .4) . Medica ion classes mos
commonly in ol ed in DRA ela ed o ea men sa e y included an i h ombo ic agen s, an-
iin lamma o y and an i heuma ic p oduc s, diu e ics and an ineoplas ic agen s. Diu e ics,
an ihype ensi es, an i h ombo ic agen s and d ugs used in diabe es ep esen ed he mos
common medica ion classes in ol ed in DRA ela ed o ea men e ec i eness . Measu -
ing he scope and na u e o DRA is essen ial o he de elopmen o isk minimiza ion
measu es . The ela i ely high p e en abili y sugges s he e is a po en ial o educe DRA
in he u u e .
The s udy was suppo ed by he G an Agency o Cha les Uni e si y (P ojec No. 14120)
and om he p ojec o Speci ic Academic Resea ch (SVV 260 551).
ADHERENCE AND BELIEFS ABOUT IMMUNOSUPPRESSANTS IN PATIENTS
AFTER KIDNEY TRANSPLANTATION: RESULTS FROM UNICENTRIC
FOLLOW-UP STUDY
KOŠŤÁLOVÁ, B.,1 MALÁ-LÁDOVÁ, K .,1 KUBĚNA, A. A.,1 HORNE, R .,2 DUSILOVÁ-SULKOVÁ, S .,3
MALÝ, J .1
1 Depa men o Social and Clinical Pha macy, Facul y o Pha macy in H adec K álo é, Cha les Uni e si y,
Czech Republic
2 Cen e o Beha iou al Medicine, UCL School o Pha macy, Uni e si y College London, Uni ed Kingdom
3 Haemodialysis Cen e, Uni e si y Hospi al H adec K álo é, Czech Republic
e-mail: anko b@ a .cuni .cz
S ic medica ion adhe ence o immunosupp essan s is essen ial du ing he whole
ime a e kidney ansplan a ion (KTx) . The e o e, he aim o ou s udy was o e alua e
sel - epo ed adhe ence and belie s abou immunosupp essan s o e ime and links wi h
clinical ou comes such as g a unc ioning and de no o malignancy . This obse a ional
s udy is a pa o he mul iphase p ojec TAKTIS (de eloping, implemen ing, and es ing

102
o an in eg a ed ca e model o adul s a e KTx) . Da a we e collec ed a he ou pa ien
pos - ansplan clinic in he Uni e si y Hospi al H adec K álo é . Adul pa ien s a leas
4 weeks a e KTx we e in i ed o he s uc u ed in e iew, ollowed by sel -adminis e ed
ques ionnai e su ey . P ima y ou comes such as adhe ence and belie s abou imunosup-
p essan s we e measu ed by alida ed in e na ional ools . Two da a collec ions conduc ed
be ween 2016 and 2019 in ol ed 134 pa ien s . Non-adhe ence o immunosupp essan s
was epo ed by 18 (13 .4%) pa ien s a he baseline and by 15 (11 .2%) a he ollow-
up . The pe cei ed necessi y o immunosupp essan s dec eased while conce ns inc eased
o e ime (p < 0 .001) . Baseline highe conce ns we e associa ed wi h he less han ull
sco e in adhe ence (p = 0 .0445) o wi h he new onse o cance . On he con a y, highe
baseline needs co esponded wi h be e kidney unc ioning . Bo h esul s emained sig-
ni ican a e adjus ing o age (p = 0.0493 and p = 0.0059, espec i ely). As a conclusion,
sel - epo ed non-adhe ence emained simila o e he epo ing pe iod and belie s abou
immunosupp essan s co esponded wi h clinical ou comes ela ed o bo h unde - and o e -
immunosupp ession .
The s udy was suppo ed om he p ojec o Speci ic Academic Resea ch (SVV 260 551).
THEORY-DRIVEN DEVELOPMENT OF A MEDICATION ADHERENCE
INTERVENTION DELIVERED BY E-HEALTH AND TRANSPLANT TEAM
IN ALLOGENEIC STEM CELL TRANSPLANTATION:
THE SMILE IMPLEMENTATION SCIENCE PROJECT
RIBAUT, J .,1,2 LEPPLA, L .,1,3 TEYNOR, A .,4 VALENTA, S .,1,2 DOBBELS, F .,1,5 ZULLIG, L . L .,6,7
De GEEST, S .1,5
1 Ins i u e o Nu sing Science, Depa men Public Heal h, Facul y o Medicine, Uni e si y o Basel,
Swi ze land
2 Depa men o Hema ology, Uni e si y Hospi al o Basel, Swi ze land
3 Depa men s o Hema ology, Oncology and S em Cell T ansplan a ion, Uni e si y Medical Cen e , F eibu g,
Ge many
4 Depa men o Compu e Science, Uni e si y o Applied Sciences, Augsbu g, Ge many
5 Academic Cen e o Nu sing and Midwi e y, Depa men o Public Heal h and P ima y Ca e,
Uni e si y o Leu en, Belgium
6 Depa men o Popula ion Heal h Science, Duke Uni e si y, Du ham (NC), USA
7 Cen e o Inno a ion o Accele a e Disco e y and P ac ice T ans o ma ion (ADAPT),
Du ham Ve e ans A ai s Heal h Ca e Sys em, Du ham (NC), USA
e-mail: jane e . ibau @unibas .ch
Medica ion adhe ence o immunosupp essan s in allogeneic s em cell ansplan a ion
(alloSCT) is essen ial o achie e a o able clinical ou comes .1 O e 600 apps suppo -
ing medica ion adhe ence exis , ye hey lack success ul implemen a ion likely because
o lack o end-use in ol emen and heo e ical unde pinnings in hei de elopmen and
insu icien a en ion o implemen a ion me hods o suppo he use in eal-li e. Medica-
ion adhe ence has 3 phases: ini ia ion, implemen a ion and pe sis ence .2 We epo he
heo y-d i en de elopmen o a medica ion adhe ence in e en ion (implemen a ion and
103
pe sis ence phase) in alloSCT pa ien s as a i s s ep o u u e digi iza ion and imple-
men a ion in clinical se ing wi hin he SMILe p ojec (De elopmen , implemen a ion and
es ing o an in eg a ed ca e model in allogeneic S eM cell ansplan a Ion aciLi a ed by
eHeal h) .
We applied he Beha io Change Wheel (BCW) and Capabili y-Oppo uni y-Mo i a-
ion and Beha io (COM-B) model using 3 sugges ed s ages3 ollowed by one s age added
by ou eam as p epa a ion o digi iza ion o he in e en ion: (I) De ining he p oblem in
beha io al e ms, (II) Iden i ying in e en ion op ions, (III) Iden i ying con en and imple-
men a ion op ions, (IV) SMILe Ca e Model De elopmen . Scien i ic e idence, da a om
a con ex ual analysis and pa ien s’, ca egi e s’ and clinical expe s’ inpu s we e compiled
o wo k h ough hese s eps .
(I) Co ec immunosupp essan aking and iming we e de ined as a ge beha io s.
The ocus o he in e en ion was de e mined wi hin he COM-B dimensions Capabili y
(e.g. lack o ou ine), Oppo uni y (e.g. lack o cues) and Mo i a ion (e.g. lack o p oblem
sol ing) . (II) Fi e in e en ion unc ions we e chosen, such as educa ion, aining and ena-
blemen . (III) Twen y- ou beha io change echniques we e selec ed, e.g. ac ion planning
and p oblem sol ing . (IV) Finally, 17 use s o ies we e de eloped o guide he SMILeApp’s
so wa e de elopmen p ocess .
Ou example on he heo y-d i en de elopmen o an eHeal h powe ed in e en ion in
alloSCT using a igo ous 3+1-s age app oach based on BCW, COM-B and agile so wa e
de elopmen , can be used as me hodological guidance o o he eHeal h in e en ion de-
elope s . Ou app oach has he po en ial o enhance he success ul implemen a ion and
sus ained used o eHeal h solu ions in eal-li e .
The s udy was suppo ed by he Uni e si y o Basel, Swi ze land.
Re e ences
1 . GRESCH, B ., KIRSCH, M ., FIERZ, K . e al .: Bone Ma ow T ansplan ., 52, 2017, 304–306 .
2 . VRIJENS, B ., De GEEST, S ., HUGHES, D . A . e al .: B . J . Clin . Pha m ., 73, 2012, 691–705 .
3 . MICHIE, S ., Van STRALEN, M . M ., WEST, R .: Implemen . Sci ., 6, 2011, a . 42 .
ASSOCIATION OF MATERNAL ANTHROPOMETRIC PARAMETERS
AND NUTRITION WITH MILK PRODUCTION DURING LACTATION
NAJPAVEROVÁ, S .,1 KOVAŘÍK, M.,1 KAČEROVSKÝ, M.,2 ZADÁK, Z .,3 HRONEK, M .1,2
1 Depa men o Biological and Medical Sciences, Facul y o Pha macy in H adec K álo é, Cha les Uni e si y,
Czech Republic
2 Depa men o Obs e ics and Gynecology, Uni e si y Hospi al H adec K álo é, Czech Republic
3 Biomedical Resea ch Cen e, Uni e si y Hospi al H adec K álo é, Czech Republic
e-mail: najpa es@ a .cuni .cz
Human b eas milk is a unique sou ce o newbo n nu i ion and p o ides a balanced
p o ile o nu ien s. Ou s udy is ocused on he e alua ion o ma e nal an h opome ic
pa ame e s, mainly a - ee mass (FFM), adipose issue mass, body mass index (BMI), and
104
in ake o nu i ional ene gy and mac onu ien s (NEMI) wi h espec o b eas milk p oduc-
ion in Czech women, especially a he end o p egnancy and du ing he nine mon hs a e
pa u i ion . Fi y-one heal hy Czech p egnan women ( olun ee s om p ena al cou ses
o Uni e si y Hospi al H adec K álo é) we e en olled o his s udy . Measu emen s we e
done in he las p egnancy pe iod (36 h–38 h ges a ional week) and in ou lac a ion phases
(3 weeks and 3, 6, 9 mon hs pos pa um) . Se en-day nu i ional eco ds we e assessed by
he p og am Nu iDan . The bioimpedance spec oscopic me hod was applied o body
composi ion analysis . The milk sample was sucked by b eas pump a e 6 hou s o non-
b eas eeding . Da a showed a posi i e co ela ion be ween NEMI and milk olume (MV)
du ing he ou pe iods pos pa um . A he end o p egnancy, p o ein in ake was posi i ely
associa ed wi h FFM (p < 0 .05) . G ea e ep esen a ion o ma e nal FFM is ela ed o
highe MV p oduc ion . Women’s adiposi y and BMI nega i ely co ela ed wi h MV . In
women wi h BMI abo e 28 kg m‒2 a he end o p egnancy milk p oduc ion was educed
below 1 .5 mL pe kg o women body weigh 3 weeks a e pa u i ion .
The s udy was suppo ed by he G an Agency o Cha les Uni e si y (P ojec
No. 1306218), by Minis y o Heal h, Czech Republic – concep ual de elopmen o e-
sea ch o ganiza ion (UHHK, 00179906), by he Resea ch p og amme De elopmen and
S udy o D ugs (P og es Q42) and om he p ojec o Speci ic Academic Resea ch (SVV
260 551).
PERSISTENCE WITH LIPID LOWERING MEDICINES IN SLOVENIA
DVOŘÁČKOVÁ, S.,1 MALÝ, J .,1 LOCATELLI, I .,2 KOS, M .2
1 Depa men o Social and Clinical Pha macy, Facul y o Pha macy in H adec K álo é, Cha les Uni e si y,
Czech Republic
2 Depa men o Social Pha macy, Facul y o Pha macy, Uni e si y o Ljubljana, Slo enia
e-mail: d o acsi@ a .cuni .cz
Lipid lowe ing medica ions, speci ically he hyd oxyme hylglu a yl-coenzyme A e-
duc ase inhibi o s (s a ins), a e conside ed o be one he mos equen ly used medica ions
in Eu ope as well as in he Uni ed S a es .1 The insu icien medica ion pe sis ence may
lead o decompensa ed lipidemia o ca dio ascula e en s, ela ed heal hca e cos s and
inc eased mo ali y in pa ien s wi h hype lipidemia .2
The aim o his s udy was o pe o m d ug u iliza ion analysis o s a ins (alone o in
combina ions) be ween 2015 and 2019 and o assess he medica ion pe sis ence in a coho
o pa ien s who inicia ed he he apy in 2015 and con inued un il 2019 . Fo his pu pose
he Slo enian heal h claims da a on p esc ip ion medicines we e applied . The da abase
was ob ained om he Heal h Insu ance Ins i u e o Slo enia and con ained pa ien ’s and
physician’s demog aphy, da e o e ill, numbe o d ug packages e illed and numbe o
de ined daily doses (DDD) pe package. Medicine consump ion was compu ed as numbe
o DDD pe housand inhabi ans pe day (DDD/TID). Discon inua ion gap was de ined
as mo e han 135 days wi hou medica ion e ill. The analysis was conduc ed using IBM
SPSS, e . 26 and MS Excel .
105
The p elimina y esul s show ha he o al annual numbe o s a in p esc ip ions and
pa ien s inc eased du ing he s udy pe iod om 796,514 o 890,940 and om 229,543 o
254,842 (cca 13% o Slo enian popula ion), espec i ely . The pa ien s du ing he s udy
pe iod comp ised a e agely 50 .3% males and he mean age was 68 .3 yea s . The o al
consump ion o s a ins was 621.33 DDD/TID, highes consump ion was egis e ed o
osu as a in (361.79 DDD/TID) and a o as a in (179.83 DDD/TID). The s udy coho
o new pa ien s on he apy in yea 2015 con ained 30,111 pa ien s (who ecei ed 317,877
p esc ip ions in he pe iod 2015–2019), 68 .7% o hese ecei ed a leas one p esc ip ion
in 2016 . The discon inua ion gap was cap u ed in 38,067 pa ien s be ween 2015–2019 . The
ongoing esul s a e o be expec ed .
Since he wo ldwide popula ion is expec ed o age and he mos o he s a ins a e a ail-
able in gene ic e sions, use o s a ins he apy could also simul aneously inc ease,1 which
would be a co ne s one o u he esea ch and ocus o impo ance o op imal medica ion
pe sis ence .
The s udy was suppo ed om he p ojec o Speci ic Academic Resea ch (SVV 260 551)
and ERASMUS+.
Re e ences
1. MORTENSEN, M . B ., FALK, E ., SCHMIDT, M .: Ci c . Ca dio asc . Qual . Ou comes ., 10 (7), 2017, e003811 .
2. DESHPANDE, S ., QUEK, R . G ., FORBES, C . A . e al.: Cu . Med . Res . Opin ., 33, 2017, 769–778 .
PHARMACEUTICAL CARE IN GHETTO THERESIENSTADT 1942–1945
ARNDT, T .
Depa men o Social and Clinical Pha macy, Facul y o Pha macy in H adec K álo é, Cha les Uni e si y,
Czech Republic
e-mail: a nd @ a .cuni .cz
Today he e m “pha maceu ical ca e” includes an indi idual app oach o he pa ien ,
o ien a ion o he pa ien ’s pha maco he apy, and d ug p oblems. Howe e , his de ini-
ion is applicable e en in he speci ic condi ions o he heal h ca e sys em o he ghe o
The esiens ad .1 This wo k aims o iden i y medicamen s in he ghe o heal h ca e sys em .
The in o ma ion was a ailable om he a chi es o he Jewish Museum in P ague . The
key documen s da e om 1944–1945 . The in o ma ion ecei ed will be analyzed om he
poin o iew o dosage o m, p oduce , coun y o o igin, he ac i e ing edien , he apeu ic
indica ions e c . I compa e he analysis wi h he heal h and social si ua ion in he ghe o .2
In his way, I ha e comple ely analyzed he documen In en o y o he d ug wa ehouse in
The esiens ad and o e iews o d ug deli e ies3 and pa ly g oup 13 o he so-called “ e-
ceip s” (Receip No. 152–277, conce ning medicines in The esiens ad ). F om he i s o
hese, I iden i ied 332 d ugs (manu ac u ed in pha maceu ical ac o ies), 34 pha maceu i-
cal excipien s, and 40 plan d ugs. I ha e no iden i ied 52 d ugs ye . O he dosage o ms,
he e we e mos able s and d agees (116 pieces), injec ions (89), and oin men s and c eams
(22) . The g oups o analgesics (28), d ugs o women’s diseases (22), and chemo he apeu-
112
Albendazole (ABZ) is an an helmin ic d ug used o ea men and con ol o gas-
oin es inal nema odes in small uminan s . A e he ea men , he exc emen s con ain
esiduals o he d ug and i s me aboli es and i no handled p ope ly hey en e he en i on-
men . Howe e , he subsequen a e o his d ug in he en i onmen is poo ly moni o ed .
Ou p ojec e eals he ci cula ion o ABZ in he eal a m condi ions. The ield wi h
odde plan s was e ilized wi h exc emen s o ea ed sheep con aining ABZ esiduals .
The g own plan s we e ed o in ec ed sheep o wo weeks . A e wa ds, we ha e de ec ed
aces o ABZ in he plan s, sheep umen con en , plasma and he exc emen s, p o ing he
ci cula ion o his en i onmen ally pe sis en d ug .
Fu he mo e, he e ec o de ec ed sub-le hal doses o ABZ and he me aboli es on
he pa asi es and he hos was moni o ed . The RNA was isola ed om li e o sheep ex-
posed o albendazole doses p esen in odde plan s om he e ilized ield o 14 days
and e e se ansc ibed . Indi idual mRNAs encoding cy och ome P450 iso o ms (CYPs)
and UDP-glucu onosyl ans e ase we e quan i ied by eal- ime polyme ase chain eac ion
(RT-qPCR) and he da a we e e alua ed by compa a i e del a-C me hod . Resul s showed
ha ABZ in e y low dose signi ican ly inc eased CYP1A2 mRNA and dec eased CYP3A4
mRNA in sheep . In conclusion, he ch onic e ec o e en e y low doses o ABZ p esen
in he en i onmen may enhance i s me abolism when p ope dose adminis e ed, hence
cause he ine ec i e ea men and acili a e he de elopmen o esis ance in helmin hs .
The s udy was suppo ed by he Czech Science Founda ion (P ojec No. 18-07724S)
and om he p ojec o Speci ic Academic Resea ch (SVV 260 550).
THE EFFECT OF PYRAZINE DERIVATIVE ON SECONDARY METABOLITES
CONTENT IN PLANT CULTURE OF SILYBUM MARIANUM (L .) GAERTN
IN VITRO
BLAHNOVÁ, K., TŮMOVÁ, L.
Depa men o Pha macognosy, Facul y o Pha macy in H adec K álo é, Cha les Uni e si y, Czech Republic
e-mail: blahno k@ a .cuni .cz
The aim o his wo k was o de e mine he e ec o an abio ic elici o om he class o
py azine de i a es 1-benzyl-3-(py azin-2-yl)u ea on he p oduc ion o seconda y me abo-
li es (SM) in he plan cul u e Silybum ma ianum (L .) Gae n .1 Elici a ion was pe o med
on bo h callus and suspension cul u es . The elici o was used in h ee di e en concen a-
ions. Pa icula samples we e aken a e 6, 24, 48, 72 and 168 hou s o elici o in luence.
A e d ying, he callus and suspension issues we e ex ac ed wi h me hanol and he con-
en o he moni o ed seconda y me aboli es was de e mined by HPLC . I was also es ed
i SM a e eleased in o he g ow h medium . Fla onolignans silybinin A and silybinin B
we e no de ec ed in any o he analyzed samples . The highes p oduc ion o SM was
achie ed a e elici a ion o suspension cul u es . Maximum alues o he con en we e
eached by la onoid axi olin. The mos signi ican inc ease o he con en was de e mined
a silych is in in callus cul u es. Only silydianin was eleased in signi ican amoun s in o

113
he g ow h media o he cul u es . I was shown ha he elici o 1-benzyl-3-(py azin-2-yl)
u ea is able o inc ease he p oduc ion o SM in bo h callus and suspension cul u es o
milk his le in ce ain concen a ions and du a ion o ac ion has an e ec on he exc e ion
moni o ed me aboli es in o he nu ien medium .
The s udy was suppo ed om he p ojec o Speci ic Academic Resea ch (SVV 260 550).
Re e ences
1. DOLEŽAL, M., KRÁLOVÁ, K. Syn hesis and E alua ion o Py azine De i a i es wi h He bicidal Ac i i y. In
He bicides, Theo y and Applica ions. La amendy, M. L., Soloneski, S. (eds.) In echOpen, 2011, pp. 581‒610.
AMARYLLIDACEAE ALKALOIDS AS MODEL STRUCTURES
FOR THE DEVELOPMENT OF NEW POTENTIAL DRUGS
KNÁPKOVÁ, S ., HULCOVÁ, D .
Depa men o Pha macognosy, Facul y o Pha macy in H adec K álo é, Cha les Uni e si y, Czech Republic
email: knapko s@ a .cuni .cz
The amily Ama yllidaceae includes a la ge numbe o gene a o lowe ing plan s as
Hippeas um, Na cissus o Zephy an es. All o hem con ain speci ic Ama yllidaceae
alkaloids, which a e cha ac e is ic o his amily due o hei chemical s uc u es . The
disco e y and s udy o hese alkaloids has a ac ed a en ion o many scien is s due o he
di e se biological ac i i y o hese compounds, o example cy o oxic, an icholines e ases,
an ibac e ial, an i i al .1 Plan s o he genus Hippeas um ha e been used in adi ional
medicine o ea umo s and in lamma o y diso de s. This use can be explained by he
alkaloids, which i con ains . I is mainly lyco ine, haeman amine and panc is a ine . These
compounds ha e an an i umo e ec . The species Hippeas um c . Fe a i is u he ich
in he alkaloid i a ine . In some esea ch, simple semisyn he ic de i a i es o haeman-
hamine displayed p omising inhibi o y ac i i ies agains cholines e ases . Fo his eason,
i a ine was chosen as nex lead-s uc u e o p epa a ion o semisyn e ic de i a i es .2
Se en new de i a i es we e p epa ed by es e i ica ion o he alkaloid i a ine and wo
we e c ea ed in he o m o e he s. All o hem we e iden i ied by NMR and HRMS analy-
sis . Subsequen ly, he abili y o he de i a i es o inhibi human ace ylcholines e ase and
bu y ylcholines e ase (BuChE) was s udied . Mos o he p epa ed de i a i es showed
good inhibi o y po en ial agains BuChE . The bes o hem shown ac i i y wi h IC alues
1 .39 ± 0 .08 µM .
The s udy was suppo ed by EFSA CDN (Reg. No. CZ.02.1.01/0.0/0.0/16_019/0000841)
co- unded by ERDF and om he p ojec o Speci ic Academic Resea ch (SVV 260 548).
Re e ences
1. CAHLÍKOVÁ, L., LOČÁREK, M., CHLEBEK, J. e al.: Na . P od. Commun., 8, 2013, 781‒785.
2. AL SHAMMARI, L., HULCOVÁ, D., MAŘÍKOVÁ, J. e al.: S. A . J. Bo ., 136, 2021, 137‒146.
114
INDOLE ALKALOIDS FROM VINCA MINOR AND THEIR BIOLOGICAL
ACTIVITY
ČEŘOVSKÁ, E.,1 KOHELOVÁ, E .,1 MAŘÍKOVÁ, J.,2 HULCOVÁ, D .,1 CHLEBEK, J .1
1 ADINACO Resea ch G oup, Facul y o Pha macy in H adec K álo é, Cha les Uni e si y, Czech Republic
2 Depa men o O ganic and Bioo ganic Chemis y, Facul y o Pha macy in H adec K álo é,
Cha les Uni e si y, Czech Republic
e-mail: ce o sel@ a .cuni .cz
Vinca mino L . is an e e g een pe ennial plan belonging o he Apocynaceae amily .
Phy ochemical sc eening o i s biologically ac i e cons i uen s e ealed a wide ange o
indole alkaloids (IAs) . To da e, mo e han 50 IAs ha e been epo ed in V. mino .1 Se e al
o hese indole alkaloids, such as incamine, a e equen ly used as a emedy due o hei
ce eb o asodila o y and neu op o ec i e ac i i y . In addi ion, some bisindole alkaloids
such as inca ubine, exhibi ema kable ac i i y on leukemic cell lines .1,2
The summa y e hanolic ex ac was p epa ed om d ied ae ial plan s o V. mino (63 kg)
and sepa a ed by commonly used ch oma og aphic echniques (column ch oma og aphy,
lash ch oma og aphy, p epa a i e TLC). So a , ou alkaloids ha e been ob ained om
wo ac ions. The isola ed IAs we e iden i ied by compa ison o ob ained analy ical da a
(MS, NMR, op ical o a o y) wi h he li e a u e da a. The alkaloids isola ed in a su icien
quan i y we e assayed o hei biological ac i i ies connec ed o Alzheime ’s disease (inhi-
bi ion o cholines e ases, inhibi ion o p olyloligopep idase, abili y o c oss he blood-b ain
ba ie ) and an icance po en ial (cy o oxici y agains panel o umo and leukemic cell
lines). Signi ican cy o oxic ac i i y was demons a ed by a no el bisindole alkaloid named
inca e ugine .
The s udy was suppo ed om he p ojec o Speci ic Academic Resea ch (SVV 260 548).
Re e ences
1. ABOUZEID, S ., HIJAZIN, T ., LEWERENZ, L . e al .: Phy ochemis y, 168, 2019, 1‒9.
2. PROKSA, B., GROSSMANN, E.: Phy ochem. Anal., 2, 1991, 74‒76.
ISOLATION OF ALKALOIDS FROM NARCISSUS POETICUS a . RECURVUS
AS POTENTIAL DRUGS IN THE TREATMENT OF ALZHEIMER’S DISEASE
HASANOVÁ, S ., HULCOVÁ, D .
Depa men o Pha macognosy, Facul y o Pha macy in H adec K álo é, Cha les Uni e si y, Czech Republic
e-mail: hasano s@ a .cuni .cz
Plan s o he Ama yllidaceae amily a e known o con ain a speci ic ype o compounds,
namely he Ama yllidaceae alkaloids . Among hese alkaloids, he mos impo an one is
galan hamine ha is app o ed o he pha macological ea men o Alzheime ’s disease
(AD) .1 AD is he mos p e alen neu odegene a i e disease wo ldwide wi h complex e i-
115
ology and mul i ace ed pa hophysiology . Based on he a ious causa i e ac o s o AD,
se e al hypo heses, including choline gic, amyloid, τ-p o ein, calcium dyshomeos asis,
and isop enoid change, ha e been pu o wa d . Focused on he choline gic hypo hesis,
a de ici o he neu o ansmi e ace ylcholine (ACh) in he co ex esul s in a cogni i e
de e io a ion . ACh le els can be main ained ia inhibi ion o ace ylcholines e ase .2 Impo -
an sou ce o Ama yllidaceae alkaloids men ioned abo e is he genus Na cissus . Ex ac
om Na cissus poe icus a . ecu us was sc eened a he Depa men o Pha maceu ical
Bo any o he i s ime in 2013.3 Subsequen phy ochemical esea ch began wi h 29 kg
o esh bulbs om which 42 g o alkaloid ex ac was ob ained . Abou 6 g o lyco ine was
isola ed om his ex ac . The es o he ex ac was e alua ed o i s alkaloid p o ile by
GS/MS and HPLC. This was ollowed by sepa a ion using lash ch oma og aphy. Finally,
18 ac ions we e ob ained which in u n we e e alua ed by GS/MS and HPLC. Indi idual
ac ions a e p ocessed by p epa a i e TLC .
The s udy was suppo ed by EFSA-CDN (Reg. No. CZ.02.1.01/0.0/0.0/16_019/0000841)
co- unded by ERDF and om he p ojec o Speci ic Academic Resea ch (SVV 260 548).
Re e ences
1. CAHLÍKOVÁ, L., LOČÁREK, M., CHLEBEK, J. e al.: Na . P od. Commun. 8, 2013, 781‒785.
2. HULCOVÁ, D., MAŘÍKOVÁ, J., KORÁBEČNÝ, J. e al.: Phy ochemis y, 165, 2019, a . 112055 .
3. HRSTKA, V.: Neu o opní a an ioxidační ak i i a yb aných d uhů jednoděložných alkaloidních os lin IV
(Neu o opic and an ioxidan ac i i y o selec ed species o monoco yledonous plan s con aining alkaloids IV) .
Diploma hesis, Facul y o Pha macy in H adec K álo é, Cha les Uni e si y, 2013 .
MONITORING OF ALBENDAZOLE TRANSFER FROM OVINE FAECES
TO FODDER PLANTS
SOCHOVÁ, A ., NAVRÁTILOVÁ, M ., SKÁLOVÁ, L .
Depa men o Biochemical Sciences, Facul y o Pha macy in H adec K álo é, Cha les Uni e si y,
Czech Republic
e-mail: socho aan@ a .cuni .cz
Albendazole (ABZ) belongs o a benzimidazole g oup o an helmin ic d ugs . These
d ugs a e egula ly and equen ly used o limi and ea pa asi ic in ec ions in animals . In
his way, he consump ion o hese d ugs inc eases and hei nega i e e ec s on non- a ge
o ganisms and he en i onmen is ex ended .1
We know ha he plan s can up ake and e en bio ans o m he ABZ in labo a o y-con-
olled condi ions .2 The p esen s udy moni o s he ans e o ABZ and i s ans o ma ion
p oduc s (TPs) om he aeces o ea ed sheep o common odde plan s Medicago sa i a
and T i olium p a ense . We wan ed o know i he e is a possibili y o ans e ing hese
compounds in o soil and plan s in eal ield condi ions.
Ou s udy success ully e ealed he occu ence o ABZ TPs (ABZ-SO and ABZ-SO2)
in odde plan s. E en wo mon hs a e he i s con ac o odde plan s wi h aeces,
ABZ-SO was s ill p esen . The highes concen a ion o TPs was obse ed in he 1s and
116
2nd week a e he applica ion o aeces . Then, he amoun o TPs in plan s dec eased du -
ing he ime, excep in May, whe e a sligh inc ease was obse ed, p obably due o highe
p ecipi a ion . The p esence o he TPs in odde plan s ep esen s no only a dange o
he bi o ous in e eb a es, bu also may play an addi ional ole in he de elopmen o ABZ
esis ance in helmin hs .
The s udy was suppo ed by he G an Agency o Cha les Uni e si y (P ojec
No. 1136120) and om he p ojec o Speci ic Academic Resea ch (SVV 260 550).
Re e ences
1. DOBŠÍKOVÁ, R., ŠIROKÁ, Z.: Fa makologie p odukci po a in a ezidua léči po a inách (Pha macol-
ogy in ood p oduc ion and d ug esidues in ood) [online] . B no, Ve e iná ní a a maceu ická uni e zi a B no,
2014 .
2. RAISOVÁ STUCHLÍKOVÁ, L., NAVRÁTILOVÁ, M., LANGHANSOVÁ, L. e al .: In . J . Mol . Sci . 21,
2020, a . 5943 .
SEMI-SYNTHETIC DERIVATIVES OF β-CARBOLINE ALKALOID HARMINE
AND THEIR BIOLOGICAL ACTIVITY
FEJTKOVÁ, M .,1 KOHELOVÁ, E .,1 CHLEBEK, J .,1 MAŘÍKOVÁ, J.,2 HULCOVÁ, D .1
1 Depa men o Pha maceu ical Bo any, Facul y o Pha macy in H adec K álo é, Cha les Uni e si y,
Czech Republic
2 Depa men o O ganic and Bioo ganic Chemis y, Facul y o Pha macy in H adec K álo é,
Cha les Uni e si y, Czech Republic
e-mail: ej ko ma @ a .cuni .cz
Alzheime ’s disease (AD) is a se ious and i e e sible p og essi e neu odegene a i e
diso de , ha will each a p e alence o mo e han 100 million by 2050 due o he aging
o popula ion. The main pa hological hallma ks o AD a e in acellula neu o ib illa y an-
gles, ex acellula amyloid plaques, inc eased oxida i e s ess and choline gic dys unc ion .
Choline gic neu o ansmission is e mina ed by ace ylcholine hyd olysis egula ed by wo
enzymes: ace ylcholines e ase (AChE) and bu y ylcholines e ase (BuChE) .1,2
Alkaloids play an impo an ole in he ea men o AD . Well-known Ama yllidaceae
alkaloid galan hamine is a ma ke ed d ug o AD he apy unde he comme cial name Remi-
nyl© .1 β-Ca boline alkaloid ha mine, isola ed om Peganum ha mala (Ni a iaceae), lacks
any signi ican ac i i y agains human cholines e ases. Howe e , se e al new de i a i es o
H3CO
ha mine
N
H
N
CH3
B
R
H3CO CH3
N
N
R
117
ha mine p epa ed by he N-9 de i a iza ion showed in e es ing inhibi ion BuChE . Newly
p epa ed compounds we e iden i ied by NMR and ESI-MS me hods. The mos ac i e com-
pounds will be s udied in mo e de ail (e.g . ype o inhibi ion, docking s udies, logBB e c .) .
The s udy was suppo ed om he p ojec o Speci ic Academic Resea ch (SVV 260 548).
Re e ences
1. AL MAMUN, A., MAŘÍKOVÁ, J., HULCOVÁ, D. e al .: Biomolecules, 10, 2020, a . 800 .
2. KOŠAK, U., BRUS, B., KNEZ, D. e al.: J. Med. Chem., 61, 2018, 119‒139.
GILTERITINIB AS OCT1 INHIBITOR AND SUBSTRATE: POTENTIAL
FOR DRUG-DRUG INTERACTIONS?
NOVOTNÁ, K., ŠORF, A., ČEČKOVÁ, M.
Depa men o Pha macology and Toxicology, Facul y o Pha macy in H adec K álo é, Cha les Uni e si y,
Czech Republic
e-mail: no o naka e@ a .cuni .cz
Gil e i inib is one o he ecen ly app o ed d ugs which is p ima ily used in he ea -
men o elapsed/ e ac o y acu e myeloid leukemia (AML) wi h mu a ed FMS-like
y osine kinase 3 (FLT3) ecep o . In his p ojec , gil e i inib was in es iga ed in e ms o
i s abili y o in e ac wi h solu e ca ie s (SLC) memb ane anspo e s, namely wi h OCT1
and OCT2 . These memb ane p o eins play a ole in up ake o endogenous compounds
and also d ugs in o he cells o main elimina ion o gans (li e , kidney), bu also o cance
cells . In pa icula , we wan ed o examine po en ial in e ac ion wi h dauno ubicin, a d ug
adi ionally used in AML he apy . Fi s , we pe o med accumula ion s udy and e alua ed,
whe he gil e i inib is po en ial inhibi o o OCT1 s udying di e en ial up ake o dauno-
ubicin in o MDCKII-OCT1 cells based on OCT1 inhibi ion by gil e i inib . Secondly, he
s udy e alua ing he ans e o gil e i inib ac oss he monolaye s o MDCKII-OCT1 and
con ol MDCKII-VK cell lines was conduc ed o es gil e i inib as a po en ial subs a e
o his anspo e . The ob ained da a showed ha gil e i inib has abili y o inhibi he
OCT1-media ed anspo o dauno ubicin in o he MDCKII-OCT1 cells . This e ec was
no obse ed nei he in con ol cell line, no MDCKII-OCT2 cells . We u he obse ed en-
hanced basola e al- o-apical anspo o gil e i inib ac oss monolaye s o MDCKII-OCT1
cells compa ed o MDCKII-VK cells . This di e ence was abolished in he p esence o
OCT1 inhibi o , sugges ing ha gil e i inib is a subs a e o OCT1 . Resul s ob ained in ou
s udy indica e ha gil e i inib migh be p one o OCT1-media ed pha macokine ic d ug-
d ug in e ac ions . The hypo hesis ha combina o y ea men o AML wi h gil e i inib
and dauno ubicin could esul in dec easing a ailabili y o he d ugs o he leukemia cells
leading o lowe e icacy o he ea men should be e i ied.
The s udy was suppo ed by he Resea ch p og am Pha macokine ic mechanisms o
d ug esis ance in acu e myeloid leukemia, hei a ec ing and egula ion (PRIMUS/20/
MED/010) and om he p ojec o Speci ic Academic Resea ch (SVV 260 549).

118
NEW INHIBITORS OF TOPOSIOMERASE II – STUDY
OF ANTIPROLIFERATIVE EFFECTS AND THEIR INFLUENCE
ON ANTITUMOR ACTIVITY OF ETOPOSIDE
OHNEMICHLOVÁ, L., KUBEŠ, J., ŠIMŮNEK, T.
Depa men o Biochemical Sciences, Facul y o Pha macy in H adec K álo é, Cha les Uni e si y,
Czech Republic
e-mail: ohnemicl@ a .cuni .cz
Cance is a se ious socie al heal h p oblem, which can a ec each o us, and i s inci-
dence inc eases apidly wi h age . An h acycline an ibio ics (ANT) a e ex emely e ec i e
d ugs ha ha e been used o ea a numbe o cance s, namely b eas cance , small cell
b onchogenic cance , ecu en o a ian cance and many mo e . They ha e a mul imodal
mechanism o ac ion, one o hem is he inhibi ion o opoisome ase II (TOP2), an essen-
ial cellula enzyme modula ing DNA opology . Cu en ly, use o ANTs is limi ed due o
conce ns abou he occu ence o ca dio oxici y . E oposide (ETO) is an an i umo agen
ha ac s as opoisome ase poison . ETO is o en used in combina ion he apy wi h ANTs,
bu i is no conside ed ca dio oxic . Dex azoxane (DEX) is he only app o ed ca diop o-
ec an agains ca dio oxici y o ANTs . Howe e , i does no ac as chela ing inhibi o ,
as p e iously hough , bu h ough inhibi ion o TOP2 . Al hough DEX has been shown
o be a e y po en ca diop o ec an , i also has i s disad an ages . I has been associa ed
wi h he occu ence o seconda y malignancies, mos o en wi h acu e myeloid leukemia,
less wi h myelodysplas ic synd ome, acu e lymphoblas ic leukemia o non-Hodgkin’s
lym oma . Hence, i is necessa y o examine o he agen s .1 The aim o he s udy was o
de e mine whe he o he inhibi o s o TOP2, namely (BNS-22, XK-469, ICRF-193) can
a ec an ip oli e a i e e ec o ETO on he HL-60 leucemic cell line . Fo he es ed
agen s, concen a ions co esponding wi h hei IC50 we e de e mined and on he basis o
his concen a ion hei an ip oli e a i e e ec s we e e alua ed bo h alone and in combi-
na ion wi h ETO . Fo de e mina ion o cell iabili y, MTT aasay was used . The esul s
seem p omising and some o he agen s e en show syne gis ic e ec in combina ion wi h
ETO .
The s udy was suppo ed by he Czech Science Founda ion (P ojec No. 18-08169S)
and by he G an Agency o Cha les Uni e si y (P ojec No. 246219) and om he p ojec
o Speci ic Academic Resea ch (SVV 260 550).
Re e ences
1. VEJPONGSA, P., YEH, E. T. H.: Clin. Pha macol. The ., 95 (1), 2013, 45‒52.
119
SCREENING OF INHIBITORY ACTIVITY AGAINST CHOLINESTERASES
OF VARIOUS SPECIES OF THE GENUS FICUS II
JANOVCOVÁ, H .,1 HANUSOVÁ, A .,1 HULCOVÁ, D .,1 CAHLÍKOVÁ, L.2
1 Depa men o Pha macognosy, Facul y o Pha macy in H adec K álo é, Cha les Uni e si y, Czech Republic
2 Depa men o Pha maceu ical Bo any, Facul y o Pha macy in H adec K álo é, Cha les Uni e si y,
Czech Republic
e-mail: jano coh@ a .cuni .cz
Alkaloids a e some o he mos in e es ing subs ances o seconda y me abolism . These
compounds a e syn hesized in plan s om amino acids o hei de i a i es and con ain
ni ogen in he s uc u e ha is inco po a ed in o he e ocycle in mos cases .1 Alkaloids
exhibi a a ie y o biological ac i i ies as cy o oxic, an i-in lamma o y, an i ungal,
an imala ial o an icholines e ase . The an icholines e ase e ec s o alkaloids include
inhibi ion o human enzymes ace ylcholines e ase (AChE) and bu y ylcholines e ase
(BuChE), which can be used in he apy o Alzheime ’s disease (AD) . AD is he mos
common o m o demen ia, mani es ed by impai men o cogni i e and noncogni i e
unc ions ha e en ually lead o dea h .2 The genus Ficus belongs o he amily Mo aceae,
which is widesp ead in opical and sub opical egions o he Wes e n Paci ic a ea. Plan s
om his genus con ain la ge amoun s o subs ances, including alkaloids .3 Fo he phy-
ochemical s udy, nine ex ac s om lea es and s ems om 6 species o he genus Ficus
we e p epa ed . D y ma e ial was g ound and ex ac ed by boiling in e hanol . Then e ha-
nolic ex ac s we e pu i ied by liquid-liquid ex ac ion (e he , e hyl ace a e,chlo o o m).
All ex ac s we e es ed o hei abili y o inhibi AChE and BuChE . Only ex ac AL-
708E showed inhibi ion ac i i y agains human BuChE (53 .29 ± 0 .03% a concen a ion
50 µg mL−1) .
The s udy was suppo ed by EFSA-CDN (Reg. No. CZ.02.1.01/0.0/0.0/16_019/0000841)
co- unded by ERDF and om he p ojec o Speci ic Academic Resea ch (SVV 260 548).
Re e ences
1. HULCOVÁ, D., MAŘÍKOVÁ, J., KORÁBEČNÝ, J. e al .: Phy ochemis y, 165, 2019, a . 112055 .
2. CAHLÍKOVÁ, L., MACÁKOVÁ, K., BENEŠOVÁ, N. e al.: Chap e 6 ‒ Na u al Compounds (Small Mol-
ecules) as Po en ial and Real D ugs o Alzheime ’s Disease: A C i ical Re iew . In: S udies in Na u al P oduc s
Chemis y, Vol . 42, A a-u -Rahman (ed .), Ams e dam, Else ie , 2014, pp . 153–194 .
3. KUBO, M ., YATSUZUKA, W ., MATSUSHIMA, S . e al.: Chem. Pha m. Bull., 64, 2016, 957‒960.
SCREENING OF INHIBITORY ACTIVITY AGAINST CHOLINESTERASES
OF VARIOUS SPECIES OF THE GENUS FICUS I .
HANUSOVÁ, A ., JANOVCOVÁ, H ., HULCOVÁ, D .
Depa men o Pha macognosy, Facul y o Pha macy in H adec K álo é, Cha les Uni e si y, Czech Republic
e-mail: hanuso aan@ a .cuni .cz
120
Following scien i ic esea ch ocuses on selec ed Ficus species and hei po en ial usage
in ea men o Alzheime ’s disease (AD) hanks o alkaloids con ained in hem . AD is one
o he mos common diseases o he elde ly and one o he mos equen cause o demen-
ia . Cu en ly, AD is incu able . The only hing ha can be done is o slow down p og ession
o he symp oms . Inhibi ion o ace ylcholines e ase (AChE) and bu y ylcholines e ase
(BuChE) plays an impo an ole in his p ocess .1,2 Alkaloids a e subs ances o seconda y
me abolism ha a e usually syn hesized om amino acids o hei de i a i es and can be
ound in a ious plan o gans . Alkaloids ha e a numbe o in e es ing biological e ec s .
Fo example, galan hamine inhibi s AChE and he e o e i is used o ea men o AD .1
Plan s o genus Ficus belonging o Mo aceae amily include nea ly one housand species .
These a e e e g een ees ha can be ound mainly in opical and sub opical a eas o Wes
Paci ic. They con ain alkaloids o a ious s uc u es, which ha e an imala ial, an ibac e ial
and an icance ac i i y .3 The aim o his esea ch was o sc een se e al ex ac s as po en-
ial sou ces o subs ances o he ea men o AD . Ten ex ac s o 8 selec ed species o
genus Ficus we e subjec ed o a phy ochemical s udy . D y g inded lea es and s ems we e
ex ac ed by boiling in e hanol. Ob ained e hanol ex ac s we e pu i ied by liquid-liquid
ex ac ion using e he , e hyl ace a e and chlo o o m . All ex ac s we e es ed on he abili y
o inhibi AChE and BuChE . Abili y o inhibi BuChE showed only he ex ac AL-700C
(74 .82 ± 2 .78% a concen a ion 50 µg mL−1) .
The s udy was suppo ed by EFSA-CDN (Reg. No. CZ.02.1.01/0.0/0.0/16_019/0000841)
co- unded by ERDF and om he p ojec o Speci ic Academic Resea ch (SVV 260 548).
Re e ences
1. HULCOVÁ, D., MAŘÍKOVÁ, J., KORÁBEČNÝ, J. e al .: Phy ochemis y, 165, 2019, a . 112055 .
2 . HULCOVÁ, D ., BREITEROVÁ, K ., SIATKA T . e al .: Molecules, 23, 2018, a . 719 .
3. KUBO, M ., YATSUZUKA, W ., MATSUSHIMA, S . e al .: Chem. Pha m. Bull., 64, 2016, 957‒960.
MONITORING THE SPREAD OF ALBENDAZOLE FROM THE SHEEP FAECES
IN AGRICULTURAL LAND BY LC-MS
VRÁBĽOVÁ, D., NAVRÁTILOVÁ, M., SKÁLOVÁ, L.
Depa men o Biochemical Sciences, Facul y o Pha macy in H adec K álo é, Cha les Uni e si y,
Czech Republic
e-mail: abldan@ a .cuni .cz
The an helmin ic d ug albendazole (ABZ) wi h a b oad-spec um an helmin ic e -
ec is used o he ea men o helmin hiasis caused mainly by gas oin es inal wo ms
in e e ina y and human medicine . F equen dose, o e dose o unde dose make a isk o
de eloping esis ance, which can be a se ious global p oblem in he ea men o helmin-
hiasis . The an helmin ics can en e he en i onmen unchanged as a pa en compound o
as a me aboli e h ough he aeces o ea ed animals . These chemicals can be abso bed in o
plan s, soil and g oundwa e and hey can ha e a nega i e impac on he li e and g ow h
o smalle o ganisms .
121
This expe imen aimed o moni o he dis ibu ion o albendazole and i s ans o ma ion
p oduc s (TPs) albendazole sul oxide (ABZ-SO) and albendazole sul one (ABZ-SO2) om
he aeces o ea ed domes ic sheep in ag icul u al land . This was obse ed om di e en
dis ances and dep hs o which he compounds could sp ead . In gene al, he concen a ion
o he compounds in he soil was g ea e in he opsoil han in he bo om laye and close
o he aeces . We also obse ed he dependence o changes in subs ance concen a ion on
ain all (d y and ainy mon hs) . The pa en d ug and TPs we e ex ac ed om soil using
he solid-phase dispe sion ex ac ion (QuEChERS) and iden i ica ion and quan i ica ion
we e done by UHPLC-MS .
The s udy was suppo ed by he G an Agency o Cha les Uni e si y (P ojec
No. 1136120) and om he p ojec o Speci ic Academic Resea ch (SVV 260 550).
Re e ences
1. PRCHAL, L ., PODLIPNÁ, R ., LAMKA, J . e al.: En i on . Sci . Pollu . Res ., 23, 2016, 13015–13022 .
THE EFFECTS OF TOPOISOMERASE II BETA ON THE SENSITIVITY
OF THE CANCER CELLS TO THE ANTINEOPLASTICS
JAŠČEVSKÁ, N., SKALICKÁ, V., JIRKOVSKÁ, A.
Depa men o Biochemical Sciences, Facul y o Pha macy in H adec K álo é, Cha les Uni e si y,
Czech Republic
e-mail: jasce sn@ a .cuni .cz
Topoisome ase II is a cellula enzyme esponsible o sol ing opological p oblems
o double-s anded DNA. Topoisome ase IIα and IIb iso o ms a e a ious gene p oduc s
ha ing conse ed ca aly ic ac i i ies. The TOP IIα iso o m is p esen in p oli e a ing cell,
while TOP IIb iso o m is p edominan ly p esen in non-p oli e a ing cells, especially neu-
ons . An h acycline an ibio ics a ge ing TOP IIb a e cu en ly among he mos e ec i e
an icance d ugs . The main ac o limi ing hei clinical use is he de elopmen o side
e ec s – especially myelo oxici y and ca dio oxici y . The mechanism o an h acycline-
induced ca dio oxici y is s ill no ully elucida ed . Nowadays, he mos accep ed heo y is
he abili y o an h acyclines o p oduce eac i e oxygen species damaging he hea muscle
by oxida ion . Howe e , he mechanism is p obably mul i ac o ial . Ne e heless, he key
ole o inhibi ion o he TOP IIb enzyme, which is p esen in ca diomyocy es, has been
inc easingly discussed . The only clinically used ca diop o ec i e is dex azoxane . E en
i s mechanism o ac ion is no ully unde s ood . Howe e , new s udies sugges he majo
mechanism o ac ion h ough TOP IIb loca ed in ca diomyocy es (deple ion a e dex azox-
ane exposu e) .1 The p ac ical aim o his p ojec was o in es iga e he di e ences in he
an ip oli e a i e e ec s o dauno ubicin and dex azoxane in human cell suspension line o
HL-60 umo cells wi h a ious TOP IIb exp ession . Fu he o de e mine he amoun o
TOP IIα and TOP IIb mRNA in hese cell lines by RT-qPCR and he amoun o p o ein by
immunoblo ing . P ima y sc eening o he designed p ime s a he TOP IIb enzyme mu a-
ion si e was also pe o med .
128
PREPARATION OF DENDRALENES SUBSTITUTED
WITH ELECTRON-WITHDRAWING GROUPS
ŠTEMBEROVÁ, M., BRŮŽA, Z., POUR, M.
Depa men o O ganic and Bioo ganic Chemis y, Facul y o Pha macy in H adec K álo é, Cha les Uni e si y,
Czech Republic
e-mail: s embe ma@ a .cuni .cz
Speci ic ype o b anched, c oss-conjuga ed polyenes is called dend alenes1 ( om
G eek “Dend os” – ee) . Thei s uc u e (Scheme 1, 1) which, in heo y, is no limi ed
by he numbe [n] o double bonds, is ideal o cycloaddi ion eac ions such as Diels-
Alde eac ion, in which complex polycyclic compounds can be ob ained in single s ep
(Scheme 1, 2) .
Fig. 23
Scheme 1. S uc u e and eac i i y o dend alenes
Ou goal was o p epa e new dend alenes (Scheme 2, 5), subs i u ed p edominan ly
wi h elec on wi hd awing g oups (EWG) . The p ocedu es p e iously de eloped by ou
esea ch g oup based on Migi a-S ille coupling o compounds 3 and 4 .2 Fu he mo e, hei
abili y o unde go Diels-Alde eac ion was in es iga ed (Scheme 2, 6) .
Fig. 24
Scheme 2. P epa a ion and po en ial eac i i y o EWG-[3]dend alenes
The s udy was suppo ed by he Czech Science Founda ion (P ojec No. 18-17868S)
and om he p ojec o Speci ic Academic Resea ch (SVV 260 547).
Re e ences
1. HOPF, H ., SHERBURN, M . S .: Angew . Chem . In . Ed ., 51, 2012, 2298–2338 .
2. KRATOCHVÍL, J., NOVÁK, Z., GHAVRE, M. e al .: O g . Le ., 17, 2015, 520–523 .

129
TESTING OF (−)-N-DODECYL-N-METHYLEPHEDRINIUM BROMIDE
AS A CHIRAL SELECTOR IN CAPILLARY ELECTROPHORESIS
ENANTIOSEPARATIONS
MŰLLEROVÁ, K., JÁČ, P., POLÁŠEK, M.
Depa men o Analy ical Chemis y, Facul y o Pha macy in H adec K álo é, Cha les Uni e si y,
Czech Republic
e-mail: mulle o ak@ a .cuni .cz
Chi al ionic liquid (−)-N-dodecyl-N-me hylephed inium b omide (DMEB) was es ed
as a selec o o chi al sepa a ions o selec ed d ugs such as chi al quinolones, ke op o-
en, and lu bip o en by capilla y elec opho esis (CE). The e ec o se e al pa ame e s
on enan io-sepa a ion was examined: (i) ype and pH o he sepa a ion bu e , (ii) ype
and amoun o o ganic modi ie , and (iii) he concen a ion o DMEB. When using his
chi al selec o , only he sepa a ion o o loxacin enan iome s was obse ed, while he
enan io- ecogni ion o o he chi al model analy es was no success ul unde he condi-
ions es ed .
A CE me hod o he assay o le o loxacin was de eloped o demons a e he po en ial
o DMEB as a chi al selec o in quali y con ol o single-isome d ugs . The bes sepa a ion
was achie ed wi h 20 mmol L−1 is bu e o pH 8 .5 con aining 100 mmol L−1 DMEB and
20% ( / ) o ace oni ile as he backg ound elec oly e. The sepa a ion ook place in 50 µm
id used silica capilla y (80.5 cm / 72 cm) a −30 kV wi h UV de ec ion a 291 nm. The eso-
lu ion be ween he peaks o o loxacin enan iome s was 4.22 ± 0.02 (n = 3). Linea i y o he
me hod was p o ed o he ange 10 o 100 µg mL−1 o le o loxacin (y = 0.0305x − 0.0107,
R2 = 0.9975), ga i loxacin (40 µg mL−1) was employed as in e nal s anda d . The me hod
was applied o he analysis o able s con aining 500 mg o le o loxacin. The con en de e -
mined was 100.1 ± 4.6% (n = 3) o he decla ed amoun o le o loxacin. Hence, p ospec i e
applicabili y o DMEB as chi al selec o in pha maceu ical analysis o single-isome d ugs
was demons a ed .
The s udy was suppo ed om he p ojec o Speci ic Academic Resea ch (SVV 260 548).
SYNTHESIS AND DYNAMICS OF DEUTERIUM-LABELED ACYLCERAMIDES
HAVRIŠÁK, T ., OPÁLKA, L .
Depa men o O ganic and Bioo ganic Chemis y, Facul y o Pha macy in H adec K álo é, Cha les Uni e si y,
Czech Republic
e-mail: ha isa @ a .cuni .cz
Acylce amides a e impo an componen s o skin pe meabili y ba ie whe e hey a e
esponsible o a o ma ion o he long pe iodici y lamella phase and co neocy e lipid en-
elope . These s uc u es a e indispensable o p e en ing wa e loss om human body and
pene a ion o undesi ed componen s o he en i onmen . Lowe le els o acylce amides
130
usually accompany skin diseases like pso iasis and a opic de ma i is . Al hough acylce a-
mides a e essen ial o p ope skin ba ie unc ion, li le is known abou hei dynamics in
skin . One o he me hods allowing us o s udy he molecula dynamics is solid-s a e NMR,
which equi es molecules wi h pa ial o comple e deu e a ion .
In his p ojec , we decided o syn hesize acylce amides wi h deu e a ion in hei ul a-
long (32 ca bons) chain . Fi s , he syn hesis was op imized using 1H compounds and based
on his op imiza ion, deu e a ed acylce amides will be p epa ed . The syn hesis s a ed om
bu y olac one and 1,12-dib omododecane which a e comme cially a ailable in hei deu-
e a ed o m . These s a ing compounds we e ans o med in o a phosphonium sal and an
aldehyde o Wi ig eac ion, p o iding a 16-ca bon agmen (p o ec ed ω-hyd oxyla ed
unsa u a ed acid), which a e a modi ica ion unde wen a second Wi ig eac ion o c e-
a e he 32-ca bon long chain. This p ecu so was hen es e i ied wi h linoleic acid and
connec ed o a sphingoid base o o m a inal molecule o acylce amide. The op imized
syn hesis using 1H compounds was pe o med in 13 s eps wi h app oxima ely 15% o e all
yield, opening he possibili y o syn hesize acylce amides wi h deu e a ion in hal o he
ul along chain (Fig . 1) . In simila manne , acylce amides wi h deu e a ion in o he hal o
he chain will be p epa ed .
The s udy was suppo ed by he Czech Science Founda ion (P ojec No.19-09135J) and
om he p ojec o Speci ic Academic Resea ch (SVV 260 547).
SYNTHESIS AND IN VITRO CARDIOPROTECTIVE ACTIVITY
OF DEXRAZOXANE ANALOGUES
MACUŠ, M ., ROH, J ., KARABANOVICH, G .
Depa men o O ganic and Bioo ganic Chemis y, Facul y o Pha macy in H adec K álo é, Cha les Uni e si y,
Czech Republic
e-mail: macusm@ a .cuni .cz
An h acylines (ANTs) as dauno ubicin, doxo ubicin, e c ., a e used as an i-cance
d ugs . ANTs ha e a s ong an i- umo e ec . Un o una ely, a limi ing ac o o ANTs
use in clinical p ac ice is hei se ious ca dio oxici y . This side e ec can lead o hea
ailu e ia i e e sible damage o hea muscle cells . The only clinically app o ed d ug
used agains ANTs-induced ca dio oxici y is bisdioxopipe azine de i a i e dex azoxane
Fig. 25
Fig. 1. S uc u e o acylce amides wi h deu e a ion in hal o he ul along chain
131
(DEX) . Mechanism o ac ion o DEX is in ensi ely in es iga ed and he e a e s ill wo
main heo ies: i) chela ion o in acellula i on ions ha p o ec s hea h agains oxida i e
damage, ii) inhibi ion/deple ion o opoisome ase IIβ in ca diomyocy es. Syn hesis and
ho ough e alua ion o new DEX de i a i es should help o cla i y DEX s uc u e–ac i -
i y ela ionship .
This s udy aimed a he p epa a ion o a DEX analogue wi h a modi ied linke (EMD).
The syn hesis o he a ge compound s a ed om pen ane-2,3-dione and he e we e 6
mo e s eps ha lead o e y h o and h eo o ms o 2,3-diaminopen ane-N,N,N′,N′- e aace ic
acid, ha we e sepa a ed by column ch oma og aphy in he o m o e aes e s. The inal
s eps consis ed o he cycliza ion o bisdioxopipe azine ings. Bo h inal dias e eome ic
p oduc s (EMDa and EMDb) we e s udied o hei abili y o chela e i on ions, o inhibi
TOPIIβ and o p o ec ca diomyocy es agains ANT oxici y. The esul s o his wo k con-
ibu e o he s udy o DEX mechanism o ac ion and o he disco e y o new and mo e
e ec i e ca diop o ec i e d ugs .
The s udy was suppo ed om he p ojec o Speci ic Academic Resea ch (SVV 260 547).
MONITORING OF LIBERATION TESTS FOR THE RELEASE
OF CLOTRIMAZOLE FROM NANOFIBERS
ERNEST, R., HÁKOVÁ, M., SKLENÁŘOVÁ, H.
Depa men o Analy ical Chemis y, Facul y o Pha macy in H adec K álo é, Cha les Uni e si y,
Czech Republic
e-mail: e nes a@ a .cuni .cz
The s udy was ocused on he analysis o elease p o iles o clo imazole om di e -
en ypes o nano ibe s using non-sepa a ion low echnique, sequen ial injec ion analysis
(SIA). Finding ideal condi ions o sa u a ion o he ibe s wi h a solu ion o clo imazole
was ano he goal. Nano ibe s we e p oduced a he Technical Uni e si y o Libe ec. Two
ypes o nano ibe ca ie s – polyme ic (polydioxanone and polycap olac one) and ino -
ganic (silica) – we e employed. Pa o he ibe o polydioxanone and polycap olac one
was sa u a ed di ec ly du ing p oduc ion in di e en a ios o monome and clo imazole .
The sa u a ed ibe s we e hen analyzed in he labo a o y. The second pa o polydiox-
Fig. 26
Fig. 1. S uc u e o DEX and syn hesis o DEX analogue EMD
132
anone and polycap olac one oge he wi h ino ganic nano ibe s was p oduced in a pu e
s a e, i.e., wi hou he ac i e subs ance. These ibe s we e es ed in he labo a o y o sa u-
a ion wi h an e hanolic solu ion o clo imazole a a ce ain concen a ion o a ce ain
ime . The sa u a ion condi ions we e changed du ing he wo k o closely moni o he ela-
ion be ween he sa u a ion condi ions and he eleased concen a ion o clo imazole . The
measu emen s we e pe o med unde well-de ined condi ions ha simula ed in ac heal hy
human skin a he empe a u e o 32 °C and pH o he bu e solu ion o 4 .5 . Unde hese
condi ions, nano ibe memb anes wi h bound clo imazole we e placed in 3 F anz cells
connec ed in pa allel o a single SIA sys em and libe a ed le els o clo imazole in he ac-
cep o medium we e moni o ed o 135 min . Samples we e aspi a ed om his medium in
egula 15 min in e als in o a SIA sys em and he con en o clo imazole was de e mined
online using UV-VIS de ec ion. The esul ing elease p o iles o clo imazole om indi-
idual nano ibe s we e compa ed. The main moni o ed pa ame e s we e he elease a e
o clo imazole in o he accep o medium, he concen a ion and he libe a ion p o ile o
clo imazole . Mo e de ailed esul s will be discussed in he p esen a ion .
The s udy was suppo ed om he p ojec o Speci ic Academic Resea ch (SVV 260 548).
SYNTHESIS OF WATER-SOLUBLE ANALOGUES
OF N-SUBSTITUTED 1,2,4-TRIAZOLES
WITH HIGH ANTIMYCOBACTERIAL ACTIVITY
VOLFOVÁ, G .,1 STOLAŘÍKOVÁ, J.,2 ROH, J .,1 KARABANOVICH, G .1
1 Depa men o O ganic and Bioo ganic Chemis y, Facul y o Pha macy in H adec K álo é,
Cha les Uni e si y, Czech Republic
2 Labo a o y o Mycobac e ia and Tube culosis, Ins i u e o Public Heal h in Os a a, Czech Republic
e-mail: ol o ag@ a .cuni .cz
Recen ly, i was shown ha 3,5-dini ophenyl-1,2,4- iazoles ha e high ac i i y agains
suscep ible and d ug- esis an s ains o Mycobac e ium ube culosis wi h he minimum
inhibi o y concen a ion o 0 .06–1 µM .1 Thus, his wo k aimed a he syn hesis o i e
wa e -soluble de i a i es o 3,5-dini ophenyl- and 3-ni o-5- i luo ome hylphenyl-
1,2,4- iazoles . The syn hesis o 4,5-subs i u ed-1,2,4- iazole-3- hiols s a ed om
co esponding hyd azides and alkyl iso hiocyana es ollowed by cycliza ion o ob ained
hiosemica bazides in aqueous po assium hyd oxide (Scheme 1) . The alkyla ion o
1,2,4- iazole-3- hiols wi h pipe idine o pipe azine con aining alkyla ion agen s esul ed
in i e inal compounds in mode a e yields (39–67%). Mo eo e , h ee by-p oduc s we e
isola ed .
All p epa ed compounds we e e alua ed o hei an imycobac e ial ac i i ies agains
M. ube culosis My 331/88, M. a ium My 330/88 and M. kansasii My 235/80. The cu en
wo k con ibu ed o he disco e y o wa e -soluble compounds wi h high e iciency ha
could be subjec ed o in i o e alua ion .
133
The s udy was suppo ed om he p ojec o Speci ic Academic Resea ch (SVV 260 547).
Re e ences
1. KARABANOVICH, G ., DUŠEK, J ., SAVKOVÁ, K . e . al .: J . Med . Chem ., 62, 2019, 8115–8139 .
EVALUATION OF POSTANTIBIOTIC EFFECT AND POSTANTIBIOTIC
SUB-MINIMUM INHIBITORY CONCENTRATION EFFECT
OF CONVENTIONAL ANTI-INFECTIVE DRUGS ACTING
AGAINST METHICILLIN-RESISTANT STAPHYLOCOCCUS AUREUS
FIALOVÁ, K., KONEČNÁ, K., JANĎOUREK, O.
Depa men o Biological and Medical Sciences, Facul y o Pha macy in H adec K álo é, Cha les Uni e si y,
Czech Republic
e-mail: [email p o ec ed]
An imic obial esis ance is a global, mul i ace ed phenomenon wi h se e e conse-
quences, including complica ed ea men , heal h cos , and highe mo ali y . The e o e, his
si ua ion needs o be p ope ly e lec ed.1 The esea ch and disco e y o new an i-in ec i es
ep esen one o he op ions o comba ing his phenomenon . A wide ange o pa ame e s is
de e mined in p eclinical s udies o new candida e an i-in ec i e compounds . Among hem,
he pos an ibio ic e ec (PAE) and pos aan ibio ic sub-minimum inhibi o y concen a ion
(PAE-SME) should be e alua ed . PAE and PAE-SME a e impo an pa ame e s o an ibi-
o ic ac ion, widely used as a p edic o o pha macodynamic ac i i y .2
In ou s udy, we ha e e alua ed PAE and PAE-SME o h ee con en ional an ibio -
ics, namely cip o loxacin, ancomycin and linezolid, ac ing agains me hicillin- esis an
S aphylococcus au eus . A compu e ized incuba o Biosc een C was employed in he s udy
o he wo pa ame e s men ioned abo e . Fo PAE e alua ion, bac e ia we e exposed o
h ee di e en inal concen a ions o d ugs (5×, 10× and 20× MIC), and in he s udy o
pa ame e PAE-SME, he subinhibi o y concen a ion co esponding o 0 .1×, 0 .2×, 0 .4×,
0 .6×, and 0 .8× MIC we e chosen o e alua ion .
The s udy was suppo ed by he Czech Science Founda ion (P ojec No. 20-19638Y).
Fig. 27
Fig. 27
Fig. 27
Scheme 1. Syn hesis o a ge isubs i u ed 1,2,4- iazoles

134
Re e ences
1. FRIEDMAN, N . D ., TEMKIN, E ., CARMELI, Y .: Clin . Mic obiol . In ec ., 22, 2016, 416–422 .
2. CHEN, H ., LI, L ., LIU, Y . e al .: In ec . D ug Resis ., 11, 2018, 2107–2115 .
CREATION OF A VIRTUAL LIBRARY OF SYNTHETIC COMPOUNDS
AND ITS PRACTICAL USAGE FOR DOCKING WITH ALDOSE REDUCTASE
VÁVROVÁ, J., KUČEROVÁ-CHLUPÁČOVÁ, M.
Depa men o Pha maceu ical Chemis y and Pha maceu ical Analysis, Facul y o Pha macy
in H adec K álo é, Cha les Uni e si y, Czech Republic
e-mail: a o aji @ a .cuni .cz
D ug de elopmen is a p ocess equi ing he analysis o a la ge amoun o da a .1 C ea ing
a i ual da abase o syn hesized compounds p o ides access o p ima y da a conce ning
s uc u e, esul s o biological ac i i y s udies, and molecula desc ip o s necessa y o d ug-
like p edic ion . This wo k ep esen s a con inua ion o he p e ious s udy .2 Mic oso Excel
was used o c ea e he da abase, which includes di e en s uc u al ypes, e.g . py azine,
hodanine, hiazolidin-2,4-dione, and 1,2,4-oxadiazole de i a i es p epa ed in he esea ch
g oup Design and De elopmen o New An imic obial Agen s . Molecules a e so ed ac-
co ding o s uc u e-simila i y, ne e heless, we also p o ide a sp eadshee con aining all
compounds in a line-no a ion eady- o-dock o ma . To demons a e his da abase’s ac ual
usage, a molecula modelling s udy wi h enzyme aldose educ ase was pe o med using he
so wa e Molecula Ope a ing En i onmen (MOE). Aldose educ ase is he i s enzyme
in he polyol-pa hway, in ol ed in mic o ascula complica ions o diabe es . I has become
a d ug a ge o aldose educ ase inhibi o s (ARI), e.g . epal es a . The main goal o he
p ojec was o s ess he co ela ion be ween in i o and in silico s udies . The isos e ic ap-
p oach was used o p edic he binding mode and a ini y owa ds he enzyme in o de o es
he sui abili y o syn hesize new compounds in he upcoming esea ch .
The s udy was suppo ed om he p ojec o Speci ic Academic Resea ch (SVV 260 547).
Re e ences
1. PATRICK, G . L .: An In oduc ion o Medicinal Chemis y, 6 h ed ., Ox o d, Ox o d Uni e si y P ess, 2017 .
2. KEBAKUILE, L . G . B .: C ea ion and analysis o in-house da abase o py azine de i a i es wi h po en ial
an imic obial ac i i y . Diploma hesis . Facul y o Pha macy in H adec K álo é, Cha les Uni e si y, 2018 .
MODIFICATION OF CAPILLARY WALL BY GRAPHENE FOR SEPARATION
APPLICATIONS
PTÁČKOVÁ, A., KUČERA, R., LOCHMAN, L.
Depa men o Pha maceu ical Chemis y and Pha maceu ical Analysis, Facul y o Pha macy in H adec
K álo é, Cha les Uni e si y, Czech Republic
e-mail: p acko an@ a .cuni .cz
135
Capilla y elec opho esis (CE) is a highly e icien sepa a ion me hod. Subs ances a e
sepa a ed due o di e en mobili y in an elec ic ield. The CE modes o ope a ion can be
modi ied in di e en ways, e.g . capilla y elec och oma og aphy, micella elec okine ic
ch oma og aphy .1 On he o he hand, modi ica ion o he inne wall o he capilla y is
belie ed o subs an ially imp o e bo h sepa a ion e iciency and selec i i y. G aphene (G)
is ca bon wi h a hexagonal s uc u e in o m o wo-dimensional sp2 single-a om- hick
shee s . G seems o be a sui able ma e ial o sepa a ion applica ion due o i s excellen
p ope ies such as la ge su ace a ea oge he wi h a ini y o ca bon ing s uc u es ia π-π
in e ac ions .2 Ou wo k is ocused on he modi ica ion o he capilla y wall by g aphene.
The wall o he capilla y was modi ied by he Laye -by-Laye me hod ia laye ing o di -
e en ly cha ged subs ances bounded by elec os a ic o ces .3 Chemical coa ing employing
co alen in e ac ions was pe o med as well .4 Di e en combina ions o polyme (PDDA,
PAH, PEI, APTES) and G we e used o su ace modi ica ion. Sepa a ion e iciency and se-
lec i i y o modi ied capilla ies we e s udied on he model mix u es o analy es (pa abens,
ni ophenols, ni oanilines, pu ines) . Ob ained esul s we e compa ed wi h comme cial
unmodi ied capilla y. Imp o ed sepa a ion oge he wi h p olonged in e ac ion o analy es
wi h G su ace was obse ed .
The s udy was suppo ed by he Resea ch p og amme De elopmen and S udy o D ugs
(P og es Q42) and om he p ojec o Speci ic Academic Resea ch (SVV 260 547).
Re e ences
1. LAUER, H . H ., ROZING, G . P .: A P ime , Agilen Technologies, Ge many 2014 .
2. SITKO, R ., ZAWISZA, B ., MALICKA, E .: T ends Anal . Chem ., 51, 2013, 33–43 .
3. ZHANG, J ., ZHANG, W ., BAO, T . e al .: J . Ch oma og . A, 1339, 2014, 192–199 .
4. QU, Q ., GU, C ., HU, X .: Anal . Chem ., 84, 2012, 8880–8890 .
CHOLINESTERASES INHIBITED BY NOVICHOK AGENTS – IN SILICO STUDY
OF REACTIVATION POSSIBILITIES
VEČEŘA, Z., KUČERA, T.
Depa men o Toxicology and Mili a y Pha macy, Facul y o Mili a y Heal h Sciences in H adec K álo é,
Uni e si y o De ence in B no, Czech Republic
e-mail: ece azb@ a .cuni .cz
“No ichoks” is he name o a se ies o ne e agen s (NA) de eloped in he o me So-
ie union du ing he Cold Wa . Like o he ne e agen s, No ichok agen s i e e sibly bind
ace ylcholines e ase (AChE) and p oduce a choline gic oxid ome, bu ha e highe oxici y
han olde ne e agen s .1 T ea men o poisoning caused by ne e agen s is based on oxime
eac i a o s o AChE . Mechanism o eac i a ion in ol es nucleophilic a ack (by oxime
g oup) o phospho us a om o inhibi ed AChE .2 The aim o he wo k was o de e mine
he binding ene gy o comme cially a ailable oxime eac i a o s in o ace ylcholines e ase
inhibi ed by no ichok, which could be used in he ea men o poisoning . Compu a ional
me hods such as molecula docking and molecula dynamics we e used o he s udy .
136
S uc u e o AChE inhibi ed by o ganophospha e (OP) we e chosen om RSCB PDB
(code 5HF9) and OP was eplaced (using Chime a so wa e) by 5 selec ed no ichoks
designa ed A230, A232, A234, A242 and A262 . The p o ein was p epa ed o molecula
modeling .
Fou comme cially a ailable eac i a o s (p alidoxime, obidoxime, imedoxime, HI-6)
and one expe imen al eac i a o (designa ed K203) we e selec ed as ligands . They we e
p epa ed in o docking- iendly pdbq o ma (using ChemSke ch, A ogad o and Au oDock
Tools) .
Semi lexible docking was used o de e mine he bes ligand pose a he ecep o . The
mos sui able pose was chosen as ini ial posi ion o molecula dynamics . Then complexes
p o ein-ligand we e p epa ed and molecula dynamics we e pe o med using G omacs
so wa e . We de e mined he binding ene gy o he ligands in he p o ein .
The s udy was suppo ed by he Facul y o Mili a y Heal h Sciences and om he p o-
jec o Speci ic Academic Resea ch (SVV 260 547).
Re e ences
1. NEPOVIMOVÁ, E., KUČA, K.: Food Chem. Toxicol., 121, 2018, 343–350.
2. GÓRECKI, L., KORÁBEČNÝ, J., MUSÍLEK, K. e al .: A ch . Toxicol ., 90, 2016, 2831–2859 .
SYNTHESIS OF POTENTIAL MYCOBACTERIAL INH-A
AND CHOLINESTERASES INHIBITORS BASED ON TRICLOSAN
VU, Q . A ., PFLÉGR, V ., KRÁTKÝ, M .
Depa men o O ganic and Bioo ganic Chemis y, Facul y o Pha macy in H adec K álo é, Cha les Uni e si y,
Czech Republic
e-mail: uq@ a .cuni .cz
The con ibu ion deals wi h he syn hesis and e alua ion o new inhibi o s o he
mycobac e ial InhA enzyme and inhibi o s o ace ylcholines e ase (AChE) and bu y ylcho-
lines e ase (BChE) . All o he p epa ed compounds a e analogues de i ed om iclosan,
hey could be good candida es as po en ial d ugs o use in he ea men o ube culosis and
neu odegene a i e diseases, including Alzheime ’s disease .1,2
Eigh compounds we e p epa ed in sa is ac o y yields . All o hem we e es ed o
an imic obial and cholines e ase inhibi o y ac i i y . Among all he compounds ha we
p epa ed N-[5-chlo o-2-(2,4-dichlo ophenoxy)phenyl]ace amide showed he bes an i-
mic obial e ec agains all h ee selec ed mycobac e ia. Speci ically, i had a minimum
inhibi o y concen a ion o 31 .25 mg L−1 agains M. smegma is, a minimum inhibi o y
concen a ion o 15 .625 mg L−1 agains M. au um, and a minimum inhibi o y concen a-
ion o 7 .81 mg L−1 agains M. ube culosis H37Ra . This compound also showed he lowes
IC50 alue o AChE (48.85 μmol L−1) and has a be e inhibi o y e ec agains AChE han
i as igmine (56.10 μmol L−1) . The p ecu so 5-chlo o-2-(2,4-dichlo ophenoxy)aniline
(“amino- iclosan”) showed he bes inhibi ion o BChE (IC50 = 11.93 μmol L−1), which is
a be e inhibi o y ac i i y compa ed o i as igmine again .
137
The s udy was suppo ed by he Czech Science Founda ion (P ojec No. 20-19638Y)
and om he p ojec o Speci ic Academic Resea ch (SVV 260 547).
Re e ences
1. VOSÁTKA, R ., KRÁTKÝ, M ., VINŠOVÁ, J .: Eu . J . Pha m . Sci ., 114, 2018, 318–331 .
2. KRÁTKÝ, M., ŠTĚPÁNKOVÁ, Š., VORČÁKOVÁ, K. e al .: Molecules, 21, 2016, a . 291 .
SECTION OF PHARMACEUTICAL TECHNOLOGY
EFFECT OF COMBINATION OF MUCOADHESIVE POLYMERS ON THE
BEHAVIOUR OF MATRIX TABLETS IN THE GASTRIC ENVIRONMENT
JOHNOVÁ, K., OGADAH, C. U., VRANÍKOVÁ, B.
Depa men o Pha maceu ical Technology, Facul y o Pha macy in H adec K álo é, Cha les Uni e si y,
Czech Republic
e-mail: johno aka @ a .cuni .cz
Colon- a ge ed d ug deli e y plays a signi ican ole in he pha maco he apy o local
diseases si ua ed in he la ge in es ine . In e ms o sus ained d ug elease, such o mula-
ions mus be esis an o he acidic en i onmen o he uppe gas oin es inal ac . In
addi ion, an enhanced he apeu ic e icacy may be achie ed by p olonging he esidence
ime o he o mula ion a he abso p ion si e by means o mucoadhesi e d ug deli e y
sys ems .1 Fo hese easons, he p esen ed p e o mula ion s udy in es iga es he beha iou
o ma ix able s based on mucoadhesi e polyme s in he gas ic en i onmen . Knowledge
o he beha iou o a d ug in acidic pH is impo an as he su oundings o he in lamed
colon may be lowe .
The selec ed polyme s, gua gum (GG) and hyd oxyp opyl me hylcellulose K15M
(HPMC), we e used sepa a ely o combined in a ios 85 .4 : 14 .6, 50 : 50 and 14 .6 : 85 .4 . The
iscosi y o polyme s dispe sions was e alua ed in bio ele an dissolu ion media simula ing
he gas ic en i onmen (FaSSGF) using a o a ional heome e . Subsequen ly, compac s
con aining model d ug heophylline we e p epa ed and e alua ed o hei swelling beha -
iou and dissolu ion p o iles using a USP II appa a us. The ob ained da a shows ha bo h
polyme s we e able o sus ain he d ug elease om he hyd ophilic ma ix able s o up o
24 hou s . The mix u e 14 .6 : 85 .4 seems o be he mos p omising as i o ms he s onges
gel ba ie du ing he i s wo hou s o dissolu ion. On he con a y, compac s wi h a high
amoun o GG pe o m poo ly as a p onounced bu s e ec may be obse ed due o i s apid
swelling and dissol ing o ou e , ully hyd a ed laye s in o he gas ic medium .
The s udy was suppo ed by he G an Agency o Cha les Uni e si y (P ojec No. 70119)
om he p ojec o Speci ic Academic Resea ch (SVV 260 547).
Re e ences
1. CARVALHO, F . C ., BRUSCHI, M . L ., EVANGELISTA, R . C . e al .: B az . J . Pha m . Sci ., 46, 2010, 1–17 .
144
The s udy was suppo ed by he Czech Science Founda ion (P ojec No. 19-09135J) and
om he p ojec o Speci ic Academic Resea ch (SVV 260 547).
Re e ences
1. VÁVROVÁ, K., KOVÁČIK, A., OPÁLKA, L.: Eu . Pha m . J ., 64 (2), 2017, 28–35 .
EFFECT OF COMBINATION OF MUCOADHESIVE POLYMERS
ON THE BEHAVIOUR OF MATRIX TABLETS IN THE SMALL INTESTINE
JANOUŠEK, M., OGADAH, C. U., VRANÍKOVÁ, B.
Depa men o Pha maceu ical Technology, Facul y o Pha macy in H adec K álo é, Cha les Uni e si y,
Czech Republic
e-mail: janoum@ a .cuni .cz
Colon- a ge ed d ug deli e y is highly desi able due o he di ec ea men o local
in es inal diseases, d ug dose educ ion, and minimiza ion o sys emic ad e se e ec s .
This e ec can be achie ed by se e al speci ic d ug deli e y sys ems based on di e en
mechanisms . Gene ally, he mos p e e ed a e o ally adminis e ed o mula ions due o he
ela i ely easy manu ac u ing and high adhe ence o pa ien s o ea men . These include
ma ix sys ems based on mucoadhesi e polyme s ha allow bo h a ge ing o he desi ed
si e (e.g. colon) and con olled d ug elease .1 Fo he abo e-men ioned easons, he aim o
he p esen ed s udy was o e alua e he beha io o wo mucoadhesi e polyme s, namely
gua gum, hyp omellose K15M and hei combina ions in bio ele an media simula ing
small in es ine luids (Fas ed S a e Simula ed In es inal Fluid, FaSSIF). The iscosi y o
he polyme dispe sions was measu ed using a o a ional heome e . Polyme o mula ions
(compac s) con aining he model d ug heophylline we e es ed o adhesion (modi ied
balance), swelling index (baske me hod) and dissolu ion p o iles (paddle appa a us). The
ob ained esul s sugges ed ha supe io adhesion may be expec ed in he o mula ions
con aining a highe po ion o K15M . Mo eo e , hese compac s showed also one o he
highes weigh gains a e 8 hou s o he swelling es . D ug dissolu ion was cha ac e ized
by con olled elease om all p epa ed ma ix able s o e a 24 hou ime pe iod . Fo mula-
ions con aining K15M eleased he d ug mo e cons an ly in he ini ial phase in compa ison
o he o mula ion comp ising gua gum .
The s udy was suppo ed by he G an Agency o Cha les Uni e si y (P ojec No. 70119)
and om he p ojec o Speci ic Academic Resea ch (SVV 260 547).
Re e ences
1. AMIDON, S ., BROWN, J . E ., DAVE, V . S .: AAPS Pha mSciTech, 16, 2015, 731–741 .

145
A STUDY OF COMPRESSIBILITY OF DIRECTLY COMPRESSIBLE TABLETING
MATERIALS AND TABLETS WITH CARRAGEENAN .
NÁPRAVNÍKOVÁ, M., MUŽÍKOVÁ, J.
Depa men o Pha maceu ical Technology, Facul y o Pha macy in H adec K álo é, Cha les Uni e si y,
Czech Republic
e-mail: nap a nma@ a .cuni .cz
The p esen ed communica ion deals wi h he s udy o comp essibili y o di ec ly com-
p essible able ing ma e ials wi h ι-ca ageenan.1,2 In o mula ions, ι-ca ageenan is mixed
wi h chi osan, calcium algina e and hyp omellose Me hocel K15M in he a ios o 1 : 1,
2 : 1 and 3 : 1 . The o mula ions wi h salicylic acid as a model d ug a a concen a ion o
20% and sodium s ea yl uma a e as a lub ican a a concen a ion o 1% a e also es ed .
Table s wi hou he d ug a e comp essed by comp ession o ces o 3, 4 and 5 kN . Table s
wi h he d ug a e comp essed by comp ession o ce o 5 kN and 8 kN . The comp essibili y
is e alua ed by ene gy p o ile o comp ession p ocess, ano he es ed pa ame e is ensile
s eng h o he able s . The o al ene gy o comp ession inc eases wi h he comp ession
o ce . The pa ame e is inc eased wi h he addi ion o chi osan and hyp omellose in all
a ios as well . Wi h highe p opo ion o ca ageenan in mix u es, i s alues dec ease . The
addi ion o chi osan, calcium algina e, and hyp omellose inc eases alues o he ene gy
o plas ic de o ma ion and plas ici y . The highe alues o hese pa ame e s indica e im-
p o emen o comp essibili y . Only hyp omellose in a ios o 1 : 1 and 2 : 1 o ca ageenan
inc eases he s eng h o ca ageenan able s, calcium algina e signi ican ly educes i . The
model d ug salicylic acid educes all ene gy alues and ensile s eng h o able s .
The s udy was suppo ed om he p ojec o Speci ic Academic Resea ch (SVV 260 547).
Re e ences
1 . PICKER-FREYER, K . M .: Ca ageenans in solid dosage o m design . In Pha maceu ical Dosage Fo ms –
Table s, ol . 2 . Ra ional Design and Fo mula ion, 3 d ed ., Augsbu ge , L . L ., Hoag, S . W . (eds .), Boca Ra on,
CRC P ess, 2008, 469–492 .
2. SINGH, K . K .: Ca ageenan . In: Handbook o pha maceu ical excipien s, 6 h ed ., Rowe, R . C ., Sheskey, P . J .,
Quinn, M . E . (eds .), London, Pha maceu ical P ess, 2009, 122–126 .
SECTION OF SOCIAL AND CLINICAL PHARMACY
CONSENSUS OF CZECH TERMINOLOGY IN THE FIELD OF MEDICATION
ADHERENCE
VOŘÍŠKOVÁ, E., KOŠŤÁLOVÁ, B., MALÁ, K.
Depa men o Social and Clinical Pha macy, Facul y o Pha macy in H adec K álo é, Cha les Uni e si y,
Czech Republic
e-mail: o iskoel@ a .cuni .cz
146
Due o he cons an ly changing e minology o medica ion adhe ence (MA) o e he
las 50 yea s, e ms a e o en misused in he li e a u e .1 The aim was o analyze he Czech
e minology o MA and o es ablish a consensus using a Delphi ound su ey . Czech
li e a u e ocused on he e m o MA and i s synonyms was e iewed using bibliog aphic
(PubMed, Bibliog aphia Medica Čechoslo aca) and ull- ex (Solen, P oLékaře.cz) da a-
bases . A o al o 123 a icles published be ween 1998–2020 in ol ed e ms “compliance”
(69 a icles, 57 de ini ions), “adhe ence” (78, 51), “pe sis ence” (25, 23), and “conco d-
ance” (13, 11), espec i ely. Based on he iden i ied li e a u e, a lis o panelis s who we e
in i ed o he Delphi ound su ey as sugges ed by ABC Taxonomy2 was c ea ed . This
axonomy de e mines 7 e ms and hei de ini ions in he ield o MA. Ou o 106 con-
ac ed panelis s, 46 esponded o he i s ound du ing which consensus o 2 de ini ions
om 7 e ms in he e minology o MA was es ablished . Fu he ounds a e an ongoing
p ocess and he es o he e ms and de ini ions will be de e mined. The disuni y o using
he e minology o MA and ela ed e ms showed up as a e y common phenomenon o
he Czech language . A consensus o Czech e minology will be es ablished a e he las
ound o Delphi su ey .
The s udy was suppo ed om he p ojec o Speci ic Academic Resea ch (SVV 260 551).
Re e ences
1 . VRIJENS, B ., De GEEST, S ., HUGHES, D . A ., e al.: B . J . Clin Pha macol ., 73, 2012, 691–705 .
2. ESPACOMP, P e e ed Me hods o T ansla ion o he ABC Taxonomy o Medica ion Adhe ence. h ps://
www.espacomp.eu/wp-con en /uploads/2020/08/P e e ed-Me hods- o -T ansla ion-o - he-ABC-Taxonomy
- o -Medica ion-Adhe ence-31_7_20-FINAL .pd
TRICYCLIC ANTIDEPRESSANTS CONSUMPTION IN THE CZECH REPUBLIC
KVĚTENSKÁ, Z., HORKÝ, P.
Depa men o Social and Clinical Pha macy, Facul y o Pha macy in H adec K álo é, Cha les Uni e si y,
Czech Republic
e-mail: k e ensz@ a .cuni .cz
T icyclic an idep essan s a e one o he oldes g oups o an idep essan s . Excep o
indica ion o dep ession, hey a e used in he he apy o ch onic pain o enu esis noc u na
in child en. Nowadays, icyclic an idep essan s a e d ugs o he i s choice only in some
ypes o neu opa hic pain, and in o he indica ions hey ha e been eplaced by newe
subs ances wi h a lowe occu ence o side e ec s. The aim o his wo k is o ind ou
how u iliza ion o icyclic an idep essan s has de eloped and wha sha e in u iliza ion o
an idep essan s hey ep esen . Da a o his wo k we e ob ained om he S a e Ins i u e
o D ug Con ol o he Czech Republic, namely om dis ibu o s’ epo abou supplies
o medicinal p oduc s o pha macies and heal hca e acili ies, selle s o selec ed medicinal
p oduc s, o he dis ibu o s and e e ina y doc o s . U iliza ion was e alua ed o he pe iod
om 1.1.2008 o 31.12.2018 wi h DUR (d ug u iliza ion e iew). Fo e alua ion, a de ined
daily dose pe 1000 inhabi an s pe day and me hods o desc ip i e s a is ics we e selec ed .
147
A sligh dec ease o u iliza ion o icyclic an idep essan s was obse ed o he wa ched
pe iod, as well as dec ease in hei sha e on an idep essa ns u iliza ion . The eason o he
dec ease could be he side e ec s o icyclic an idep essan s o hei possible in e ac ions
wi h o he d ugs .
The s udy was suppo ed om he p ojec o Speci ic Academic Resea ch (SVV 260 551).
RATIONALITY OF BZD USE IN PHARMACY PRACTICE IN SPAIN
AND IN DIFFERENT SETTINGS OF CARE IN THE CZECH REPUBLIC: RESULTS
FROM THE INOMED AND THE EUROAGEISM H2020 PROJECTS
MAGÁTOVÁ, A .,1 MODAMIO, P .,2 BRKIĆ, J.,1 BRAUN-VIVES, J .,2 MARIŇO, E. L.,2
LUKAČIŠINOVÁ, A.,1 REISSIGOVÁ, J .,3 FIALOVÁ, D .,1,4
1 Depa men o Social and Clinical Pha macy, Facul y o Pha macy in H adec K álo é, Cha les Uni e si y,
Czech Republic
2 Clinical Pha macy and Pha maceu ical Ca e Uni , Depa men o Pha macy and Pha maceu ical Technology
and Physical Chemis y, Facul y o Pha macy and Food Sciences, Uni e si y o Ba celona, Ba celona, Spain
3 Depa men o S a is ical Modeling, Ins i u e o Compu e Science o he Czech Academy o Sciences,
P ague, Czech Republic
4 Depa men o Ge ia ics and Ge on ology, 1s Facul y o Medicine in P ague, Czech Republic
e-mail: maga o a@ a .cuni .cz
The aim o he s udy was o compa e he p esc ip ion o BZDs in Spanish (SP) and
Czech (CZ) sample o olde adul s. Da a o 260 SP communi y- esiding senio s 65+ and
o 1602 CZ senio s 65+ we e p ospec i ely collec ed in he Eu oAgeism H2020 p ojec
in 2018–2019 (by Comp ehensi e Ge ia ic Assessmen ) and analyzed using desc ip-
i e s a is ics (R-so wa e, e sion 4 .0 .3) . In SP and CZ (communi y pha macy samples),
he e we e 62 .4% and 64 .6% o women and he mean age o pa icipan s was 71 .74
+/− 6.25 yea s and 76.61 +/− 7.15 yea s, espec i ely. Polypha macy and excessi e poly-
pha macy we e documen ed in 24 .9% and 3 .8% (p < 0 .001) (CZ) and in 41 .2 % and 13 .1%
(p < 0 .001) (SP) o olde adul s . 36 .2% o senio s used a leas one BZDs in SP compa ed
o 4 .9% in CZ (p < 0 .001) . Top 3 mos equen ly p esc ibed BZDs we e (in SP): lo az-
epam (16 .5%), lo me azepam (6 .5%) and alp azolam (4 .6%), (in CZ): alp azolam (1 .1%),
b omazepam (0 .7%) and oxazepam (0 .4%) . In Spain, ex ensi ely high p e alence o BZDs
in olde adul s (35 .4%, p < 0 .001), wi h expec ed po en ial nega i e consequences, was
ound in compa ison wi h communi y pha macy p ac ice in CZ (2 .4%, p < 0 .001), acu e
ca e (18 .0%, p < 0 .001) and ambula o y ca e (16 .7%, p < 0 .001) .
The s udy was suppo ed by InoMed (P ojec No. CZ.02.1.01/0.0/0.0/18_069/00100
46, 2019-2022) co- unded by he Eu opean Union, he EUROAGEISM H2020-MCSF-
ITN764632, by he Resea ch p og amme De elopmen and S udy o D ugs (P og es Q42)
(KSKF-2 Assoc. P o . Fialo á), om he p ojec o Speci ic Academic Resea ch (SVV 260
551), START p og amme (Reg. No CZ.02.2.69/0.0/0.0/19_073/0016935) and I-CARE-
4OLD Ho izon 2020 p ojec (G an ag eemen ID: 96534).
148
AN ANALYSIS OF DRUG INTERACTIONS BASED ON DRUG INFORMATION
CENTRE ENQUIRIES
MICHÁLEK, G., ROZSÍVALOVÁ, P., MALÁ, K.
Depa men o o Social and Clinical Pha macy, Facul y o Pha macy in H adec K álo é, Cha les Uni e si y,
Czech Republic
e-mail: michaleg@ a .cuni .cz
D ug in o ma ion cen e (DIC) o he Facul y o Pha macy in H adec K álo é, Cha les
Uni e si y and Uni e si y Hospi al H adec K álo é p o ides d ug in o ma ion o heal h-
ca e p o essionals in he o m o imely and accu a e answe s o d ug- ela ed enqui ies,
including d ug in e ac ions (DI) . This s udy aimed o analyze enqui ies ela ed o DI p o-
cessed by DIC om 2015 o 2020 . Da a we e collec ed om indi idual enqui ies ela ed
o d ug-d ug, d ug-he bal and d ug-disease in e ac ions . Va ious pa ame e s assigned o
each DI ound we e analyzed, such as clinical se e i y o ATC codes o in e ac ing d ugs .
An analysis based on desc ip i e s a is ical me hods was ca ied ou . A o al o 67 enqui -
ies we e analyzed . The h ee mos equen ATC codes being in ol ed in a leas one DI
pe enqui y we e A02BC01 (omep azole), B01AC06 (ace ylsalicylic acid), and C10AA05
(a o as a in) . Wa a in, enla axine and omep azole we e he mos equen ly in e ac ing
d ugs ega ding he di e en mechanism o in e ac ions . In con as , ci alop am, u osem-
ide, le o hy oxine and omep azole p e ailed in all in e ac ing pai s o e e y in e ac ion .
The majo i y (62%) o DI we e based on pha macodynamics, while 31% we e based on
pha macokine ics . The clinical se e i y o DI was g aded A (Mino ) in 23%, B (Mode a e)
in 67%, and C (Se e e) in 10% o cases . The mos common po en ial clinical ou comes
o DI we e inc eased isk o ad e se e ec s (18%), ele a ed plasma ic concen a ion o
a d ug (16%), and highe isk o bleeding (13%) . Addi ionally, a (s ill ongoing) quali a i e
analysis o i e enqui ies sha ing a simila clinical opic was ca ied ou . DI cons i u e
a signi ican po ion o enqui ies p ocessed by DIC and seem o di e in clinical se e i y,
pha macological mechanism and po en ial clinical ou comes .
The s udy was suppo ed om he p ojec o Speci ic Academic Resea ch (SVV 260 551).
THE PREVALENCE OF DRUG-DRUG INTERACTIONS IN PATIENTS ADMITTED
TO THE HOSPITAL VIA THE EMERGENCY DEPARTMENT
KUKRÁLOVÁ, K .,1 OČOVSKÁ, Z.,1 MAŘÍKOVÁ, M.,1,2 VLČEK, J.1,2
1 Depa men o Social and Clinical Pha macy, Facul y o Pha macy in H adec K álo é, Cha les Uni e si y,
Czech Republic
2 Depa men o Clinical Pha macy, Hospi al Pha macy, Uni e si y Hospi al H adec K álo é, Czech Republic
e-mail: kuk alok@ a .cuni .cz
The p esence o po en ial d ug-d ug in e ac ions (DDIs) is common in daily p ac ice
and only a small p opo ion o po en ial DDIs esul in hospi aliza ion o he pa ien s . Ne -
149
e heless, DDIs ep esen a signi ican cause o hospi al admissions.1 This c oss-sec ional
s udy aims o iden i y DDIs in he medica ion his o y o he pa ien s admi ed o Uni e si y
Hospi al H adec K álo é ia he eme gency depa men in Augus –No embe 2018 . The
objec i es o his s udy a e a) o de e mine he p e alence o hospi al admissions wi h
po en ial DDIs, b) o ca ego ize iden i ied po en ial DDIs wi h espec o hei mechanism,
se e i y, isk a ing, le el o documen a ion and po en ial ou comes and c) o de e mine
he p e alence o hospi al admissions wi h mani es DDIs . A sample o 375 hospi al ad-
missions has been analyzed so a . 300 hospi al admissions ha e been sc eened o he
p esence o po en ial DDIs using Mic omedex, Lexicomp and D ugAgency a . s . da abase
o d ug-d ug in e ac ions . 75 hospi al admissions ha e been excluded om he sc eening
p ocess due o an insu icien numbe o medica ions in medica ion his o y (< 2). 2273
po en ial DDIs we e iden i ied in 258 hospi al admissions (86% o he eligible admissions).
The o e all p e alence o hospi al admissions wi h iden i ied po en ial DDI in medica ion
his o y was 68 .8% (95% CI: 64 .1–73 .5) . 866 di e en DDI pai s we e in ol ed in hese
po en ial DDIs. Mani es DDIs which con ibu ed o hospi al admission we e iden i ied in
17 (4.5%) hospi al admissions. The indings will p o ide a deepe insigh in o he pha ma-
coepidemiologic aspec s o DDIs .
The s udy was suppo ed by he G an Agency o Cha les Uni e si y (P ojec No. 14120)
and om he p ojec o Speci ic Academic Resea ch (SVV 260 551).
Re e ences
1. DECHANONT, S ., MAPHANTA, S ., BUTTHUM, B . e al.: Pha macoepidemiol . D ug Sa ., 23, 2014,
489–497 .

151
2026 Folia Pha m . Uni . Ca ol . LII Pag . 151–174
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