Co esponding au ho : Douho é Gnao é Yoh Toussain
Copy igh © 2025 Au ho (s) e ain he copy igh o his a icle. This a icle is published unde he e ms o he C ea i e Commons A ibu ion License 4.0.
In silico s udy o he he apeu ic po en ial o no -cucu bi acins om Ma eya
mic an ha (Ben h) Müll. A g: An app oach on DFT heo y and ADME p edica ion
Gnao é Yoh Toussain Douho é 1, 3, *, Anoh Valen in Ablé 2, Nean ien Thile ien Yao Bi 2, Maëlle Ca az 4, 5, Ko i
Ba hélémy A ioua 2 and Soleymane Koné 2
1 Depa men o Sciences and Technologies, Uni e si y Alassane Oua a a o Bouaké, I o y Coas .
2 Depa men o Science S uc u e o Ma e and Technology, Uni e si y Félix Houphouë -Boigny, I o y Coas .
3 Cen e Suisse o Scien i ics Resea ch in I o y Coas , CSRS Km 17 oad o Dabou, I o y Coas .
4 UMR152 Pha ma De , Uni e si y o Toulouse, IRD, 31062 Toulouse, F ance.
5 Depa men o Molecula Cellula and De elopmen al Biology Uni , Cen e o Biology In eg a i e, Uni e si y o Toulouse,
CNRS, 31062 Toulouse, F ance.
Wo ld Jou nal o Ad anced Resea ch and Re iews, 2025, 27(02), 963-971
Publica ion his o y: Recei ed on 23 Ap il 2025; e ised on 31 May 2025; accep ed on 03 June 2025
A icle DOI: h ps://doi.o g/10.30574/wja .2025.27.2.2148
Abs ac
In he con ex o he alo iza ion o A ican medicinal esou ces, his s udy p oposes a heo e ical e alua ion o he
physicochemical, elec onic, he modynamic and pha macokine ic p ope ies o h ee no -cucu bi acins
(Ma mic an hine B glucoside, Ma mic an hine A glucoside, Ma mic an hine B) isola ed om Ma eya mic an ha, a
medicinal plan commonly used in I o y Coas . The analysis was ca ied ou using densi y unc ional heo y (DFT) wi h
he base 6-31++G(d,p) and ADME p edic ion ools (SwissADME). The esul s show ha he h ee compounds exhibi
good he modynamic s abili y, pa icula ly enhanced in aqueous media o Ma mic an hine A glucoside and
Ma mic an hine B, as well as a signi ican inc ease in hei pola i y (dipole momen ) in his same medium, sugges ing a
be e a ini y o biological en i onmen s. The HOMO-LUMO gaps emained high and cons an , e lec ing good
elec onic s abili y. In e ms o pha macokine ics, Ma mic an hine B glucoside and Ma mic an hine B gene ally complied
wi h Lipinski's ules and appea ed o be good candida es o o al adminis a ion, while Ma mic an hine A glucoside
showed signi ican gaps limi ing i s bioa ailabili y. These esul s indica e ha Ma mic an hine B glucoside and
Ma mic an hine B ha e p omising po en ial o u he he apeu ic de elopmen as na u al bioac i e agen s.
Keywo ds: No -cucu bi acins; DFT; SwissADME; S abili y; Reac i i y
1. In oduc ion
In I o y Coas , as in many sub-Saha an A ican coun ies, medicinal plan s ep esen no only a aluable sou ce o
ea men o a ious ailmen s, bu also an impo an economic le e o local communi ies [1]. This is he case o
Ma eya mic an ha, a Eupho biaceae commonly used in adi ional medicine o ea cons ipa ion, abdominal pain and
ce ain in ec ions caused by gas oin es inal diso de s [2], such as in es inal wo ms [3], and hemo hoids [4]. I is
egula ly used as a laxa i e [5]. This medicinal plan con ains no -cucu bi acin s e oids, which ha e been shown o ha e
an ioxidan [6], muscle elaxan [7] and an icance ac i i y on he Hep3B chemo- esis an human hepa oca cinoma cell
line [8].
In a global con ex whe e he sea ch o new he apeu ic agen s o na u al o igin is in ensi ying, pa icula ly o hei
an ioxidan , an i-in lamma o y and an icance e ec s [9], i is becoming impe a i e o enhance he alue o local
medicinal he i age h ough igo ous s udies. This is he backg ound o he p esen s udy, which aims o examine in
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dep h he p ope ies o h ee no -cucu bi acin s e oid de i a i es (Ma mic an hine B glucoside, Ma mic an hine A
glucoside, Ma mic an hine B) ecen ly isola ed om he hyd oe hanolic ex ac o Ma eya m. lea es. The
physicochemical, he modynamic, elec onic and pha macokine ic cha ac e is ics o hese compounds ha e no ye
been ully e alua ed. The gene al aim o his wo k was o e alua e, using heo e ical app oaches, he p ope ies o hese
h ee no -cucu bi acins men ioned abo e, wi h a iew o de e mining hei po en ial as candida es o d ug
de elopmen . Mo e speci ically, we analyzed hei physicochemical, elec onic and he modynamic p ope ies using
densi y unc ional heo y (DFT) wi h he 6-31++G(d,p) basis, a me hod ecognized o i s eliabili y in p edic ing
elec onic s uc u e and s abili y [10, 11], and secondly, o assess he pha macokine ic p o ile o hese compounds using
he online ool SwissADME, which allows apid and eliable p edic ion o o al bioa ailabili y acco ding o Lipinski's
ules [12, 13].
Thus, he i s phase o he s udy will ocus on:
● Calcula ing he s anda d en halpy o o ma ion (∆ H), s anda d ee ene gy (∆G°), o al ene gy (ET) and en opy
(S), in o de o assess he he modynamic s abili y o hese molecules;
● De e mina ion o he dipole momen (µD), an indica o o molecula pola i y;
● Analysis o he elec onic p ope ies by calcula ing he ene gies o he HOMO and LUMO on ie o bi als, as
well as he ene gy gap (∆Egap), he la e p o iding indica ions o he chemical eac i i y o hese compounds;
● A compa ison o he p ope ies in wo dis inc en i onmen s (gaseous and aqueous) in o de o be e
unde s and he in luence o he medium on hei s abili y.
The second phase will in ol e p edic ing he pha macokine ic p ope ies o Ma mic an hine B glucoside,
Ma mic an hine A glucoside and Ma mic an hine B using he SwissADME pla o m, based on Lipinski's ules, i.e.
molecula weigh , LogP, numbe o hyd ogen bond dono s and accep o s, wi h he aim o es ima ing hei o al
bioa ailabili y po en ial [13].
In sho , his s udy aims o p o ide a comp ehensi e and heo e ically sound unde s anding o he he apeu ic po en ial
o no -cucu bi acins om Ma eya mic an ha. Fu he mo e, his s udy con ibu es o he scien i ic de elopmen o a
widely used and s ill unde -exploi ed local na u al esou ce.
2. Ma e ial and calcula ion me hods
2.1. Ma e ial
In ou wo k, we a e in e es ed in a se o h ee bioac i e compounds (Figu e 1) om he same s uc u al amily. These
molecules we e selec ed o hei an ioxidan biological p ope ies and p omising an icance ac i i y on he chemo-
esis an human hepa oca cinoma cell line Hep3B.
Figu e 1 2D and 3D s uc u es o he s udied bioac i e compounds om Ma eya mic an ha
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2.2. Le el o heo y and calcula ion me hodology
The calcula ions we e ca ied ou using Gaussian 09 so wa e [14]. Densi y unc ional heo y (DFT) me hod was used
[15]. P e ious heo e ical wo k on he calcula ion o molecula p ope ies has shown ha hyb id unc ions such as
B3LYP and o he s, combined wi h a b oad base o unc ions, lead o alues in good ag eemen wi h expe imen al esul s
[16]. The le el o heo y chosen o his s udy is B3LYP/6-31++G(d,p).
Fi s , he h ee-dimensional s uc u es o hese h ee no -cucu bi acins, isola ed om Ma eya m., we e modeled. Thei
op imized geome ies we e hen subjec ed o densi y unc ional heo y (DFT) quan um chemical calcula ions using
Gaussian 09 so wa e wi h he B3LYP unc ional and he 6-31++G(d,p) basis. These calcula ions we e ca ied ou bo h
in he gas phase and in aqueous solu ion.
Se e al he modynamic pa ame e s, including global molecula desc ip o s, we e ex ac ed om he op imized
geome ies. These include: o al ene gy (ET), s anda d en halpy o o ma ion (Δ H), Gibbs ee ene gy (ΔG°) and en opy
(S), all de e mined a oom empe a u e (298.15 K). In pa allel, he dipole momen , an indica o o molecula pola i y,
was also calcula ed in each o he media.
In addi ion, he elec onic p ope ies, including global molecula desc ip o s and molecula eac i i y, we e analyzed.
This was made possible h ough he s udy o on ie o bi als, in pa icula he ene gy o he highes occupied o bi al
(HOMO), ha o he lowes acan o bi al (LUMO), as well as he ene gy gap (ΔEgap = ELUMO - EHOMO), conside ed o be a
de e mining pa ame e o chemical eac i i y.
Finally, pha macokine ic p ope ies we e assessed using SwissADME so wa e. This analysis was used o p edic ADME
pa ame e s (abso p ion, dis ibu ion, me abolism, exc e ion) and o check he compliance o compounds wi h Lipinski's
ules, aking in o accoun c i e ia such as molecula weigh , LogP, numbe o hyd ogen bond dono s and accep o s, as
well as opological pola su ace a ea (TPSA).
3. Resul s and discussion
3.1. Analysis o he modynamic pa ame e s
The s abili y pa ame e s examined in his se ies o compounds a e: s anda d en halpy o o ma ion (Δ H), Gibbs ee
ene gy (ΔG°), en opy (S) and o al ene gy (ET), all de e mined a oom empe a u e (298.15 K). The calcula ed alues
o said pa ame e s a e epo ed in Table 1 below.
Table 1 The modynamic desc ip o s o he s udied compounds in he gas and aqueous phases
SN.
Compounds
En i onmen
∆ H (kcal/mol)
∆G°(kcal/mol)
ET (kcal/mol)
S (J/mol.k-1)
1
Ma mic an hine B
glucoside
Gaseous
-1 517 416.02
-1 517 505.55
-1 517 416.62
300.29
Aqueous
-1 517 416.02
-1 517 505.55
-1 517 416.62
300.29
2
Ma mic an hine A
glucoside
Gaseous
-1 516 679.86
-1 516 766.94
-1 516 680.45
292.07
Aqueous
-1 516 700.83
-1 516 789.52
-1 516 701.42
297.49
3
Ma mic an hine B
Gaseous
-1 158 927.54
-1 159 001.54
-1 158 928.14
248.18
Aqueous
-1 158 942.09
-1 159 016.67
-1 158 942.68
250.14
Analysis o he he modynamic pa ame e s o he compounds Ma mic an hine B glucoside, Ma mic an hine A glucoside
and Ma mic an hine B, bo h in he gas phase and in aqueous solu ion, e eals signi ican ends in s abili y, sol en -
solu e in e ac ions and molecula o ganiza ion.
Fi s ly, en halpy o o ma ion (∆ H) and s anda d ee ene gy (∆G°) alues a e low o all compounds, indica ing
ema kable he modynamic s abili y in bo h media [17]. Howe e , Ma mic an hine A glucoside and Ma mic an hine B
alues a e obse ed o become sligh ly lowe in aqueous media, e lec ing addi ional sol a ion-induced s abiliza ion
[18]. This imp o emen can be a ibu ed o hyd ophilic in e ac ions such as hyd ogen bonds o dipole-sol en o ces
[19]. This in e ac ion is pa icula ly a o ed in he case o glycosyla ed compounds, due o he p esence o pola g oups
ca ied by he ca bohyd a e uni s, in pa icula he hyd oxyl unc ions (-OH) o glucose. These unc ional g oups
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acili a e he es ablishmen o hyd ophilic in e ac ions, such as hyd ogen bonds, wi h he aqueous sol en . In con as ,
Ma mic an hine B glucoside showed iden ical alues in he gas phase and in solu ion, sugges ing ela i e ine ia owa ds
he aqueous sol en , p obably due o a weakly pola izable s uc u e o limi ed in e ac ion wi h wa e .
In addi ion, he o al ene gies ollow he same pa e n as he en halpies, con i ming he mode a e in luence o he
sol en on Ma mic an hine A glucoside and Ma mic an hine B, while Ma mic an hine B glucoside emains i ually
unchanged. This consis ency suppo s he hypo hesis o high in insic s abili y o Ma mic an hine B glucoside,
independen o he en i onmen .
En opically, we no e ha Ma mic an hine B glucoside main ains a s able en opy (≈ 300 J/mol.K-1), sugges ing a
s uc u e ha is igid o no e y p one o eo ganiza ion in solu ion. Con e sely, Ma mic an hine A glucoside and
Ma mic an hine B show a sligh inc ease in en opy in aqueous medium (+5.42 and +1.96 J/mol.K-1, espec i ely). This
a ia ion can be explained by a con o ma ional eo ganiza ion induced by he hyd ophilic en i onmen , o e en by he
elease o wa e molecules o ganized a ound he solu e, e lec ing a mode a e en opy gain.
In sho , Ma mic an hine A glucoside and Ma mic an hine B bene i om a s abilizing e ec o he aqueous sol en , bo h
ene ge ically and en opically, making hem po en ially mo e sui able o a physiological en i onmen . On he o he
hand, he s abili y o Ma mic an hine B glucoside, al hough ema kable, seems o esul om a weak in e ac ion wi h
wa e , which could ha e a nega i e in luence on i s bioa ailabili y in a biological en i onmen . These esul s he e o e
p o ide aluable in o ma ion o he pha macochemical e alua ion o hese compounds, pa icula ly wi h ega d o
hei beha io in simula ed biological en i onmen s.
3.2. Pola i y analysis (dipole momen µD)
One o he eac i i y pa ame e s calcula ed o he s udied compounds is he dipole momen . The esul s ob ained a e
shown in Table 2.
Table 2 Dipole momen alues o he s udied compounds
SN.
Compounds
Dipole momen in he gas
phase (Debye)
Dipole momen in
aqueous phase (Debye)
1
Ma mic an hine B glucoside
6.10
8.55
2
Ma mic an hine A glucoside
5.72
8.68
3
Ma mic an hine B
5.51
8.23
E alua ion o he dipole momen o Ma mic an hine B glucoside, Ma mic an hine A glucoside and Ma mic an hine B
e ealed a signi ican inc ease in he dipole momen when mo ing om a gaseous o an aqueous en i onmen . This
inc ease in dipole momen , obse ed sys ema ically o all h ee s uc u es, e lec s an elec onic eo ganisa ion
induced by he sol en , which accen ua es he in insic pola i y o he molecules. Indeed, as a pola sol en , wa e
p omo es he s abiliza ion o he mos pola ized molecula con o ma ions, hus s eng hening solu e-sol en
in e ac ions. This phenomenon can be explained in pa icula by he sol en 's abili y o in e ac wi h he pa ial cha ges
p esen on he su ace o he molecules, leading o a p e e en ial o ien a ion o he dipoles [20].
Fu he mo e, Ma mic an hine A glucoside is dis inguished by a pa icula ly high dipole momen in aqueous solu ion.
This p ope y sugges s a high a ini y o his compound o he hyd ophilic medium, e lec ing a mo e p onounced
sol en -solu e in e ac ion. This high pola i y is likely o imp o e bo h he solubili y and he modynamic s abili y o
Ma mic an hine A glucoside in he aqueous phase, in acco dance wi h he p inciples o compa ibili y be ween solu e and
sol en pola i y. Thus, dipole momen analysis highligh s he s uc u ing in luence o he aqueous sol en on he
elec onic dis ibu ion and con o ma ional dynamics o he compounds conside ed.
3.3. Analysis o Elec onic P ope ies (HOMO, LUMO, ∆Egap)
The s abili y pa ame e s examined in his se ies o compounds a e: he ene gies o HOMO (EHOMO), LUMO (ELUMO) and
he ene gy gap o he bounda y o bi als (ΔEgap) exp essed in eV. The calcula ed alues o he said pa ame e s a e
epo ed in Table 3.
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Table 3 Ene gy desc ip o s o he s udied compounds
SN.
Compounds
En i onmen
EHOMO (eV)
ELUMO (eV)
∆Egap (eV)
1
Ma mic an hine B glucoside
Gaseous
-5.79
-1.52
4.27
Aqueous
-5.84
-1.59
4.25
2
Ma mic an hine A glucoside
Gaseous
-5.59
-1.52
4.06
Aqueous
-5.75
-1.67
4.08
3
Ma mic an hine B
Gaseous
-5.81
-1.57
4.24
Aqueous
-5.76
-1.72
4.04
In aqueous en i onmen , a sligh dec ease in he ene gies o he HOMO and LUMO on ie o bi als was obse ed o all
compounds. This mode a e dec ease sugges s a s abiliza ion o he elec onic le els by he sol en , p obably ia dipole-
dipole in e ac ions o pola iza ion e ec s induced by he elec ic ield o he sol en . Howe e , despi e his in luence,
he gap be ween HOMO and LUMO emains ela i ely cons an , indica ing ha he o e all elec onic eac i i y o he
compounds emains li le al e ed in aqueous solu ion.
Consequen ly, all compounds e ain good elec onic s abili y, e en in he p esence o he sol en , e lec ing a obus ness
o he elec onic s uc u es wi h espec o sol a ion e ec s. Howe e , i should be no ed ha Ma mic an hine A
glucoside and Ma mic an hine B ha e sligh ly lowe gaps han Ma mic an hine B glucoside, which may e lec ma ginally
highe elec onic eac i i y o hese wo compounds. Thus, al hough wa e sligh ly modula es he ene gy le els, i only
sligh ly a ec s he o e all elec onic beha io , main aining he balance be ween s abili y and eac i i y wi hin he
molecula sys ems s udied [21].
3.4. Compa ison be ween he gaseous and aqueous en i onmen s o he s udied compounds
Table 4 summa izes he main he modynamic and elec onic pa ame e s e alua ed o he h ee s udied compounds.
These pa ame e s we e analyzed in wo dis inc en i onmen s: gaseous and aqueous, in o de o be e unde s and he
impac o he sol en on hei s abili y and eac i i y. The esul s e eal ends ha a e b oadly consis en wi h he
physicochemical p ope ies expec ed o pola bioac i e molecules.
The e y low en halpies o o ma ion (∆ H) and s anda d ee ene gies (∆G°) in bo h media e lec high he modynamic
s abili y, which becomes e en mo e p onounced in he p esence o wa e , sugges ing a s abilizing e ec o sol a ion.
This s abiliza ion is also co obo a ed by a sligh inc ease in en opy, pa icula ly o Ma mic an hine B glucoside,
possibly linked o a s uc u ed eo ganiza ion induced by he hyd a ed en i onmen .
The dipole momen , an indica o o molecula pola i y, showed a signi ican inc ease in aqueous solu ion, indica ing a
g ea e a ini y o he compounds o he pola medium and an elec onic eo ien a ion a o able o he es ablishmen
o solu e-sol en in e ac ions. Finally, he alues o he HOMO-LUMO ene gy gap (∆Egap), be ween 4.0 and 4.3 eV, con i m
good elec onic s abili y, wi h li le a ia ion be ween he wo media, indica ing an o e all conse ed chemical
eac i i y.
Table 4 hus p o ides an in eg a ed o e iew o he e ec s o he sol en on he s uc u al and elec onic p ope ies o
he compounds, p o iding key elemen s o in e p e ing hei beha io in a biological en i onmen .
Table 4 Summa y o esul s ela ing o he analysis o s abili y and eac i i y pa ame e s o he s udied compounds in
gaseous and aqueous media
Pa ame e s
Gaseous En i onmen
Aqueous En i onmen
∆ H and ∆G°
Ve y weak, s able compounds
E en lowe , s abiliza ion by sol a a ion
En opy (J/mol.k-1)
Sligh ly highe (Ma mic an hine B
glucoside)
Molecula eo ganiza ion, possible s uc u ed
sol a a ion
Dipole Momen (µD)
Mode a ely pola
Inc eased pola i y, be e a ini y wi h wa e
∆Egap (HOMO-LUMO)
4.0 eV o 4.3 eV, good elec onic s abili y
Almos iden ical, so esponsi eness unchanged
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The compa a i e e alua ion in he gas and aqueous phases e eals ha he s udied compounds exhibi good
he modynamic s abili y in bo h en i onmen s. Howe e , i is impo an o no e ha he p esence o he aqueous
sol en sligh ly imp o es his s abili y, as e idenced by he lowe alues o ∆ H and ∆G°. This inc eased s abiliza ion can
be a ibu ed o speci ic sol a ion in e ac ions, such as hyd ogen bonds o dipole-dipole in e ac ions, equen ly
obse ed in hyd ophilic en i onmen s [22].
In addi ion, he ansi ion o solu ion is accompanied by a ma ked inc ease in he dipole momen o all compounds,
e lec ing inc eased molecula pola iza ion. This enhanced pola i y is o pa icula in e es in a pha macological con ex ,
as i could p omo e he in e ac ion o molecules wi h pola biological media, such as cy oplasm o blood plasma.
In e ms o elec onic eac i i y, he HOMO-LUMO gap alues emain i ually unchanged be ween he wo media,
sugges ing ha he elec onic p ope ies and chemical eac i i y o he compounds a e p ese ed in solu ion. This is a
clea ad an age in e ms o chemical obus ness in a a ie y o en i onmen s.
Finally, i should be no ed ha Ma mic an hine B glucoside has he highes he modynamic s abili y o he h ee
analyzed s uc u es, while Ma mic an hine A glucoside has he highes dipole momen in aqueous media. This la e
pa ame e sugges s a s onge in e ac ion wi h he biological en i onmen , po en ially gi ing Ma mic an hine A
glucoside g ea e e icacy in a he apeu ic con ex .
3.5. E alua ion o pha macokine ic p ope ies
Lipinski's ules (Table 5), also known as he Rule o Fi e, a e a se o c i e ia o assessing whe he a compound has a
good p o ile o o al adminis a ion, aking in o accoun i s abili y o c oss biological memb anes. Acco ding o hese
ules, good o al bioa ailabili y is likely i a leas h ee o he ollowing ou c i e ia a e me .
Table 5 Lipinski Rule c i e ia o assessing he o al pha macokine ics o compounds
C i e ia
Lipinski h eshold
In e p e a ion
Mola mass (g/mol)
≤ 500
Low mass → be e abso p ion
LogP (oc anol/wa e pa i ion coe icien )
≤ 5
Indica es lipophilici y, a good balance is equi ed
Numbe o H -bond dono s (HBD)
≤ 5
Too many dono s → poo e pe meabili y
Numbe o H-bond accep o s (HBA)
≤ 10
Too many accep o s → limi s passi e di usion
Hyd ogen bond dono s (HBD) and Hyd ogen bond accep o s (HBA)
The a ious pha macokine ic p ope y alues o Ma mic an hine B glucoside, Ma mic an hine A glucoside and
Ma mic an hine B a e shown in Table 6 below.
Table 6 Pha macokine ic p ope y alues o he s udied compounds
SN.
Compounds
Mola mass
LogP
TPSA (Ų)
HBA
HBD
Resul s
1
Ma mic an hine B
glucoside
630.81
3.58
150.59
9
4
Sligh ly high mass, bu espec s
LogP, HBD, HBA
2
Ma mic an hine A
glucoside
704.80
1.77
220.51
13
7
Mass, HBA and HBD abo e
h esholds
3
Ma mic an hine B
544.68
2.90
138.20
8
3
Mass sligh ly highe , bu wi hin he
limi s o he o he pa ame e s
Topological pola su ace a ea (TPSA)
Analysis o he physicochemical pa ame e s o he h ee s udied compounds e eals a ied p o iles wi h espec o
Lipinski's ules, which a e essen ial o p edic ing he o al bioa ailabili y o d ug candida es.
Fi s ly, al hough Ma mic an hine B glucoside has a molecula weigh abo e 500 g/mol limi , i ne e heless mee s he
o he c i e ia: i s mode a e LogP (3.58) e lec s a good hyd ophilic/lipophilic balance, while he numbe o hyd ogen
bond dono s HBD (4) and accep o s HBA (9) emain below he ecommended h esholds. In addi ion, al hough i s
opological pola su ace a ea TPSA (150.59 Ų) is ela i ely high, i emains wi hin a ange s ill compa ible wi h
Wo ld Jou nal o Ad anced Resea ch and Re iews, 2025, 27(02), 963-971
969
easonable in es inal abso p ion. As a esul , his compound can be conside ed b oadly complian wi h Lipinski's
c i e ia, despi e a sligh excess in mass.
On he o he hand, Ma mic an hine A glucoside shows se e al signi ican de ia ions om he es ablished h esholds. I s
high molecula mass (704.80 g/mol), combined wi h a high numbe o HBA (13) and HBD (7), and a e y high TPSA
(220.51 Ų), sugges limi ed memb ane pe meabili y. These p ope ies hinde o al abso p ion, making his compound
non-complian wi h Lipinski's ules. I would he e o e equi e s uc u al adjus men s o al e na i e galenic s a egies
o imp o e i s bioa ailabili y.
Finally, Ma mic an hine B is an in e es ing in e media e case. I s mola mass (544.68 g/mol) sligh ly exceeds he
ecommended h eshold, bu all o he pa ame e s a e sa is ac o y: he LogP (2.90), he HBA (8) and HBD (3) alues and
a mode a e TPSA (138.20 Ų) indica e good pha macokine ic compa ibili y. As a esul , despi e ma ginal mass
o e shoo , his compound emains Lipinski-complian , making i a p omising candida e o o al de elopmen .
Among hese h ee analyzed compounds, Ma mic an hine B glucoside and Ma mic an hine B appea o comply o e all
wi h Lipinski's ules. Indeed, al hough hei mola mass sligh ly exceeds he limi o 500 g/mol, he o he pa ame e s,
such as he LogP, he numbe o hyd ogen bond dono s (HBD) and accep o s (HBA), and he opological pola su ace
a ea (TPSA), emain wi hin he accep able anges. Consequen ly, hese sligh de ia ions, o en ole a ed in
pha maceu ical de elopmen , do no p eclude sa is ac o y o al bioa ailabili y, especially i app op ia e galenic
s a egies such as he use o nano- ec o s o p od ugs a e en isaged.
On he o he hand, Ma mic an hine A glucoside exhibi s se e al no able iola ions o Lipinski's c i e ia, including an
excessi e mola mass, a high numbe o HBD and HBA, and a pa icula ly high TPSA. These cha ac e is ics e lec a
p obably educed memb ane pe meabili y, which se e ely limi s i s po en ial o o al adminis a ion. Howe e , his
compound could e ain pha macological in e es ia al e na i e ou es o adminis a ion, such as pa en e al injec ion
o a liposomal o mula ion, making i possible o o e come he cons ain s associa ed wi h diges i e abso p ion.
4. Conclusion
The in-silico s udy conduc ed on he no -cucu bi acins Ma mic an hine B glucoside, Ma mic an hine A glucoside and
Ma mic an hine B isola ed om Ma eya mic an ha is pa o an app oach o he scien i ic alo iza ion o local medicinal
esou ces, in esponse o he g owing need o disco e new he apeu ic agen s o na u al o igin. A wo-p onged
app oach was adop ed: heo e ical analysis using densi y unc ional heo y (DFT) and pha macokine ic p edic ion using
SwissADME. This in es iga ion made i possible o cha ac e ize he physicochemical, elec onic, he modynamic and
pha macokine ic p ope ies o hese h ee no -cucu bi acin de i a i es.
The modynamically, he h ee s udied compounds we e highly s able, wi h e y low en halpy and s anda d ee ene gy
alues. The in luence o he aqueous sol en was pa icula ly bene icial o Ma mic an hine A glucoside and
Ma mic an hine B, e lec ing a be e compa ibili y wi h a biological en i onmen . On he o he hand, Ma mic an hine
B glucoside, al hough he modynamically s able, appea s o be li le a ec ed by sol a ion, which could limi i s
bioa ailabili y unde physiological condi ions.
Dipole momen analysis con i med inc eased pola iza ion in aqueous media o all he compounds, e lec ing elec onic
eo ganiza ion a o able o biological in e ac ions. Simila ly, he s udy o HOMO-LUMO on ie o bi als and he ene gy
gap e ealed mode a e chemical eac i i y, which is pa icula ly p omising o a ge ed pha macological applica ions.
Finally, ADME (Abso p ion, Dis ibu ion, Me abolism, Exc e ion) p edic ions highligh ed he compliance o he h ee
compounds wi h Lipinski's ules, wi h o e all a o able o al bioa ailabili y pa ame e s, ein o cing he idea o
exploi able he apeu ic po en ial. Ma mic an hine A glucoside and Ma mic an hine B s and ou in pa icula o hei
imp o ed solubili y and adap abili y o he physiological en i onmen .
In summa y, his heo e ical s udy p o ides a solid scien i ic basis o u u e expe imen al esea ch on no -
cucu bi acins om Ma eya mic an ha. The esul s ob ained unde line he ele ance o explo ing hem as po en ial
pha macological candida es, pa icula ly in he igh agains in lamma o y o cance ous pa hologies. The nex logical
s ep in his wo k would be o ex end he in es iga ions wi h molecula docking and dynamic simula ion s udies,
ollowed by expe imen al alida ion o he biological p ope ies iden i ied.
Wo ld Jou nal o Ad anced Resea ch and Re iews, 2025, 27(02), 963-971
970
Compliance wi h e hical s anda ds
Acknowledgmen s
The au ho s hank he e iewe s o hei insigh ul sugges ions.
Disclosu e o con lic o in e es
The au ho s decla e he e is no con lic o in e es in his s udy.
S a emen o in o med consen
In o med consen was ob ained om all indi idual pa icipan s included in he s udy.
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