*Co esponding au ho : Meena Chand an
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 Liscense 4.0.
Un eiling he an imic obial po en ial o benzimidazole de i a i es: A comp ehensi e
e iew
Meena Chand an *, Ma iya Joy, Sil ip iya K S, Anjaly M and K K ishnakuma
Depa men o Pha maceu ical Chemis y, S James’ College o Pha maceu ical Sciences and S James’ Hospi al T us
Pha maceu ical Resea ch (DSIR Recognized), Chalakudy, Ke ala, India A ilia ed o Ke ala Uni e si y o Heal h Sciences, M
G Ka u P O, Th issu , Ke ala, India.
Wo ld Jou nal o Biology Pha macy and Heal h Sciences, 2025, 23(03), 392-403
Publica ion his o y: Recei ed on 13 Augus 2025; e ised on 19 Sep embe 2025; accep ed on 22 Sep embe 2025
A icle DOI: h ps://doi.o g/10.30574/wjbphs.2025.23.3.0854
Abs ac
Benzimidazole is an impo an he e ocyclic nucleus widely explo ed o an imic obial d ug de elopmen . A b oad ange
o benzimidazole de i a i es ha e demons a ed signi ican an ibac e ial ac i i y agains bo h G am-posi i e and G am-
nega i e pa hogens, wi h se e al showing p omising e ec s agains esis an s ains. In addi ion, many de i a i es
possess no able an i ungal po en ial, being ac i e agains clinically impo an species such as Candida and Aspe gillus.
Benzimidazole-based compounds ha e also been epo ed o exhibi an ipa asi ic ac i i y, pa icula ly agains p o ozoa
and helmin hs. Owing o hei s uc u al e sa ili y and wide spec um o biological ac i i y, benzimidazole de i a i es
con inue o a ac a en ion as po en ial leads o he de elopmen o no el an imic obial agen s. This e iew highligh s
classical and ecen ad ances in he an imic obial applica ions o benzimidazole de i a i es wi h emphasis on hei
po en ial he apeu ic signi icance.
Keywo ds: Benzimidazole; Po en ial lead; S uc u al e sa ili y, Biological ac i i y, An i-mic obial agen s
1. In oduc ion
He e ocyclic compounds play a c ucial ole in mode n medicinal chemis y and among hem, benzimidazole has
eme ged as one o he mos e sa ile nucleuses. The benzene and imidazole ing sys ems used oge he o m he
he e oa oma ic nucleus benzimidazole.[1] I has long a ac ed he a en ion o medicinal chemis s due o i s s uc u al
esemblance o na u ally occu ing pu ines. Fi s syn hesized in he la e 19 h cen u y, benzimidazole and i s de i a i es
began gaining signi ican scien i ic in e es in he mid-20 h cen u y ollowing disco e ies o hei po en an helmin ic
and an imic obial p ope ies. [1,2] O e he decades, he benzimidazole sca old has e ol ed in o a p i ileged s uc u e
in d ug design, owing o i s abili y o in e ac wi h a ious biological a ge s.[3]
Benzimidazole is a bicyclic he e oa oma ic compound o med by he usion o a benzene ing wi h an imidazole ing,
ha ing he molecula o mula C₇H₆N₂. I s s uc u e is ully conjuga e wi h 10 π-elec ons, making i highly a oma ic and
plana .[3] The wo ni ogen a oms occupy posi ions 1 and 3 o he imidazole ing, wi h ca bon 2 loca ed be ween hem,
while he benzene ca bons a e numbe ed 4 o 7. [2,4]
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393
Figu e 1 S uc u e o benzimidazole
The biological applica ions o Benzimidazole nucleus we e i s iden i ied in 1944, when Woolley hypo hesized ha he
compound had a pu ine-like s uc u e and elici some biological applica ions.[5] La e on, B ink ound ha 5,6-dime hyl
benzimidazole is a i amin B12 b eakdown p oduc and ha some o i s analogues ac like i amin B12.[6] I was
o iginally syn hesized as a ungicide o plan s in he ea ly 1960s and la e as a e e ina y an helmin ic.[7] The i s
benzimidazole de eloped and app o ed o human use is Thiabendazole (1962).[8,9]
Chemically, benzimidazole exhibi s weakly basic p ope ies (pKa ≈ 5.5) and can ac as a biden a e ligand, coo dina ing
wi h me als ia i s ni ogen a oms.[10] The 2-posi ion is he mos eac i e si e o nucleophilic o elec ophilic
subs i u ion, and he benzene ing unde goes u he subs i u ion a posi ions 5–7. Alkyla ion, oxida ion, and
condensa ion eac ions a e common ans o ma ions o his nucleus.[11]
Recen yea s ha e wi nessed a su ge in he syn hesis and e alua ion o benzimidazole-based compounds, leading o he
iden i ica ion o nume ous de i a i es wi h p omising pha macological p o iles.[10] These includes an icance , an i i al,
an i-in lamma o y, an ibac e ial, an i ungal, an ioxidan , and an ihype ensi e ac i i ies, e c. S uc u al modi ica ions
a di e en posi ions o he benzimidazole co e, as well as he inco po a ion o unc ional g oups o used ing sys ems,
ha e played a pi o al ole in enhancing hese biological e ec s.[12] Ad ances in compu a ional d ug design, molecula
docking, and high- h oughpu sc eening ha e u he accele a ed he disco e y o no el benzimidazole de i a i es wi h
imp o ed selec i i y and po ency. [2,11]
O e he pas decades, esea che s ha e epo ed nume ous benzimidazole de i a i es exhibi ing po en an ibac e ial,
an i ungal, and an ipa asi ic p ope ies, making his class o compounds highly ele an in he sea ch o new an i-
mic obial agen s.[13] This e iew aims o p o ide a de ailed o e iew o he an i-mic obial ac i i ies exhibi ed by
benzimidazole de i a i es, discussing bo h classical and ecen ly epo ed compounds, while also emphasizing he
signi icance o his sca old in mode n medicinal chemis y. [13,14]
2. Benzimidazoles as an imic obial agen s
The signi icance o an imic obial ac i i y has become mo e impo an han e e as a esul o he ala ming end o
an imic obial esis ance (AMR), an immedia e global heal h conce n.[15] Excess and misuse o an ibio ics ha e esul ed
in he p oli e a ion o d ug- esis an o ganisms, ende ing p e iously ea able in ec ions a e mo e di icul o
con ol.[16] Benzimidazole de i a i es possess po en an imic obial p ope ies, e ec i ely a ge ing and dis up ing i al
cellula unc ions o bac e ia and ungi.[17] S uc u al modi ica ions on he benzimidazole sca old signi ican ly imp o e
hei ac i i y spec um and e icacy. Due o hei b oad an imic obial po en ial, hese compounds a e p omising leads
o he de elopmen o new agen s agains d ug- esis an pa hogens.[1]
Ghoneim e al., (1998) syn hesized some 2- [(4-amino o 2,4-diaminophenyl) sul onyl] de i a i es o benzimidazole
and ound ha hey possessed an ibac e ial ac i i y agains Esche ichia coli. [18]
Figu e 2 Gene al s uc u e o 2- [(4-amino o 2,4-diaminophenyl) sul onyl] benzimidazoles
4
7
5
6
N
32
NH
1
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El-mas y AH e al., (2000) iazole nucleus con aining benzimidazole de i a i es we e syn hesized. An ibac e ial,
an i ungal ac i i ies o he syn hesized compounds we e examined. The da a collec ed indica e ha compound 2 was
ound o be sligh ly ac i e agains Esche ichia coli bu e y ac i e agains Bacillus ce eus.[19]
Figu e 3 S uc u e o compound 2
Tuncbilek M e al., (2009) de eloped new benzimidazole de i a i es and e alua ed hei an ibac e ial ac i i y agains
S aphylococcus au eus, Bacillus sub ilis, Esche ichia coli, Candida albicans, and me hicillin- esis an S. au eus. The
an ibac e ial ac i i ies o compounds 24–26 we e be e han he s anda ds (cip o loxacin, ampicillin, and sul amicillin)
agains he d ug- esis an bac e ia.[20]
Figu e 4 S uc u e o compounds (24-26)
Ansa i KF e al., (2009) some new benzimidazole de i a i es we e syn hesized. All he syn he ic compounds we e
s udied o an ibac e ial ac i i y. G am-posi i e bac e ia we e posi i ely a ec ed by all he de i a i es, whe eas G am-
nega i e bac e ia we e a ec ed e y li le. Some o he syn hesized compounds exhibi ed mode a e ac i i y agains
es ed ungus.[21]
Figu e 5 Gene al s uc u e o syn hesized compounds
Ozkay Y e al., (2011) syn hesized a new se ies o benzimidazole de i a i es wi h a ying (benz)azolyl hio moie ies
and es ed hem o an imic obial ac i i y agains bac e ial s ains o E. coli 35218, E. coli 25922, P. ulga is, S.
hyphimu ium, K. pneumoniae, P. ae uginosa, L. monocy ogenes, S. au eus, E. aecalis, and B. sub ilis. Compound 5b
showed s onge an ibac e ial ac i i y agains E. coli wi h compa ed o he e e ence d ug chlo amphenicol. Compounds
5b, 5c, 5 , 5h, and 5i ha e highe an ibac e ial ac i i y agains P. ulga is.[22]
Figu e 6 S uc u e o compounds (5b, 5c, 5 , 5h & 5i)
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Ülkü Yılmaz e al., (2011) de i a i es o ime hylsilyl subs i u ed benzimidazoles we e syn hesized and es ed agains
s anda d s ains o he bac e ia G am (-) E. coli, P. ae uginosa, G am (+) E. aecalis, and S. au eus. Compound 1 possesses
he mos signi ican an ibac e ial e ec agains all o he s udied bac e ial s ains, ye i s MIC alue was always highe
han ha o he e e ence d ug ampicillin. Compounds 2 and 4 showing be e an ibac e ial ac i i y agains g am-
posi i e E. aecalis and S. au eus.[23]
Figu e 7
S uc u e o ime hylsilyl subs i u ed benzimidazole de i a i es
Chao Cong e al., (2011) se e al de i a i es o 4''-O-benzimidazolyl cla i h omycin we e syn hesized and es ed o
hei an ibac e ial ac i i y agains S. au eus ATCC25923, S. pneumoniae ATCC49619, S. pneumoniae B1, S. pneumoniae
A22072, and S. pneumoniae AB11. Compounds 16 and 17 we e mos ac i e agains e y h omycin- esis an S.
pneumoniae. Compound 17, a 2-me hoxyphenyl de i a i e, was he mos ac i e agains e y h omycin-suscep ible S.
pneumoniae ATCC496 and S. au eus ATCC25923.[24]
Figu e 8 S uc u e o 4"-O-benzimidazolyl cla i h omycin de i a i es
Jana dhana Gowda
e al., (2011) syn hesized a new class o benzimidazole subs i u ed wi h hieno- quinolines and
es ed hei an ibac e ial ac i i y agains s ains o K. pneumonia, P. ae uginosa, S. au eus, and E. coli. Ni o de i a i es
possess an ibac e ial ac i i y, bu hey a e much less ac i e han he e e ence Ni ogen u azone. [25]
Figu e 9 S uc u e o 2-(1H-benzimidazol-2-yl)-6-subs i u ed hieno[2,3-b] quinolines
Shao-Lin Zhang e al., (2012) syn hesized a numbe o benzimidazole compounds and es ed hem agains g am-
posi i e and g am-nega i e bac e ial s ains o de e mine hei an ibac e ial p ope ies. Compounds 11d and 13b show
mo e an ibac e ial ac i i y when compa ed o he e e ence d ugs luconazole, chlo omycin, and no loxacin.[26]
Figu e 10 S uc u e o compounds 11d & 13b
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Jamal K im e al., (2012) a se ies o no el benzimidazolyl we e syn hesized. All syn hesized compounds (4a–h) had
been e alua ed o in i o an ibac e ial ac i i y owa ds he subsequen bac e ial s ains; S. au eus, E. aecalis, E.
aecium, S. pneumoniae, H. in luenzae, E. coli and P. ae uginosa. Among all he compounds 4e and 4 exhibi s good
an ibac e ial ac i i y. [27]
Figu e 11 S uc u e o compound 4
Joao B Mo ei a e al., (2013) assessed he an ibac e ial e icacy o symme ic bisbenzimidazole (sBBZ) conjuga es
agains a a ie y o g am-posi i e (+) and g am-nega i e (-) bac e ial species. Addi ionally, hey disco e ed ha
de i a i es o pa a-subs i u ed e hoxy (4), amino (5), and me hoxy (9) had s ong bac e ios a ic ac ion agains Lis e ia
monocy ogenes, ancomycin- esis an en e ococci, s ep ococci, and MARS. [28]
Figu e 12 S uc u e o Symme ic Bis Benzimidazole
Nassi N Al-Mohammed e al., (2013) he imidazole de i a i es and benzimidazole de i a i es we e p oduced. The
an ibac e ial ac i i y o all syn hesized compounds was sc eened by using g am-posi i e (+) S. pyogenes, S. au eus, B.
sub ilis, R. ube , E. aecalis, and S. epide midis, as well as g am-nega i e (-) E. coli, S. yphimu ium, P. ae uginosa, and A.
calcoace ius bac e ial s ains. Compounds 3c and 9 showed highes an ibac e ial ac i i y han s anda d d ugs
amoxicillin and kanamycin.[29]
Figu e 13 S uc u e o compounds 3c and 9
Aanandhi MV e al., (2013) syn hesized a se ies o mannich bases o benzimidazole de i a i es and sc eened hei
an i ungal ac i i y agains wo ungal s ains (Aspe gillus nige , Candida albicans) and an ibac e ial ac i i y agains
di e en bac e ial s ains (B sub ilis, S au eus, E. Coli, S. yphi). Among he syn hesized compounds 3a, 3b and 3c
demons a ed signi ican an ibac e ial ac i i y and compound 3a displayed good an i ungal ac i i y han o he s.[30]
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397
Figu e 14 S uc u e o compounds 3a,3b,3c
N C Desai e al., (2014) syn hesized and es ed in i o he an ibac e ial ac i i y o a se ies o 2-py idone con aining
benzimidazole. Fo hese s udies, hey ha e used, E. coli, P. ae uginosa and wo-g am (-) S. au eus, and S. pyogenes
bac e ia. I was ound ou ha he de i a i es benzimidazole 5q and 5 's an ibac e ial ac i i ies a e compa able wi h o
some imes supe io o he e e ence d ugs cip o loxacin and chlo amphenicol. [31]
Figu e 15 S uc u e o benzimidazole de i a i es 5(a- )
Malleshappa Nool i e al., (2014) syn hesized a numbe o 1-me hyl-N-[(subs i u ed-phenylme hylidene)-1H-
benzimidazol-2-amines (4a–4g) and new aze idine-2-one de i a i es o 1H-benzimidazole (5a–5g) compounds. All o
he p oduced compounds we e es ed o cy o oxic and an ibac e ial p ope ies. S. au eus, B. pumillus, E. coli, and P.
ae uginosa we e he bac e ial s ains ha we e used. Reg e ully, as compa ed o he e e ence medica ion ampicillin,
no p oduced molecule demons a ed s ong an ibac e ial ac i i y. [32]
Figu e 16 S uc u e o compounds 4(a-g) and 5(a-g)
Yun-Lei Luo
e al.
,
(2015)
syn hesized benzimidazole de i ed naph halimide iazole de i a i es. All newly compounds
ha e been powe ul inhibi o o bac e ial s ain. Compounds 8g and 9b de i a i es a e mo e p omising o an ibac e ial
ac i i y. [33]
Figu e 17 S uc u e o compounds 8g and 9b
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Xue-Jie Fang e al., (2016) syn hesized a se ies o benzimidazoles inco po a ing 5- luo ou acil. All he syn hesized
compounds showed mode a e o excellen an ibac e ial ac i i y agains all he bac e ial s ains. The mos po en
an ibac e ial compound was compound 5c, compa ed o no loxacin and chlo omycin. [34]
Figu e 18 S uc u e o compound 5c
Na anee Singh e al., (2017) benzimidazole compounds de i ed om amino acids we e syn hesized and sc eened o
an ibac e ial ac i i y agains common s ains o S. au eus, S. pneumonia, S. pyogenes, P. ae uginosa, and K. pneumoniae.
Among he p oduced compounds, compound 2 exhibi s good an ibac e ial ac ion agains all bac e ial s ains han he
e e ence d ug e y h omycin. [35]
Figu e 19 S uc u e o compound 2
L R Singh e al., (2017) syn hesized a new se o 11 couma in-benzimidazole hyb id compounds and sc eened o hei
an ibac e ial ac i i y agains 9 bac e ial s ains o g am (+) (B. sub ilis, B. ce eus, S. au eus) and g am (-) bac e ia (P.
ae uginosa, P. ulga is, K. pneumoniae, E. coli). Compound 12 has no able ac ion agains B. sub ilis, S. au eus, P.
ae uginosa, and E. coli. Compound 14 has no able ac i i y agains P. ulga is and B. sub ilis. P. ulga is is signi ican ly
inhibi ed by compounds 16, 17, 18, 21, and 22
.
[36]
Figu e 20 Gene al s uc u e o Couma in-Benzimidazole Hyb id
N.S. El-Goha y e al. (2017) A se ies o benzimidazole compounds we e sc eened o an ibac e ial ac i i y. Compounds
14-16 we e ound o be mo e e ec i e agains S. au eus in he in es iga ed se ies. The bes an i ungal analog agains
Candida albicans was compound (14). Also, compound (16) displayed p omising ac i i y agains A. umiga us 293.
Ampicillin and luconazole we e he e e ence d ugs. [37]
Figu e 21 S uc u e o compounds 14, 15, 16
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Fonkui TY e al., (2019) syn hesized benzimidazole con aining schi base de i a i es and de e mined minimum
inhibi o y concen a ion (MIC) and minimum ungicidal concen a ion (MFC) o syn hesized schi bases, agains 14
human pa hogenic bac e ia (8 G am nega i e and 6 G am posi i e) and 7 ungal s ains (5 Aspe gillus and 2 Fusa ium).
Compound 3.c demons a ed he highes ungicidal ac i i y.[38]
Figu e 22 S uc u e o compound 3.c
Ma inescu M e al, (2020) syn hesized no el chi al benzimidazole mannich bases. All he syn hesized compounds we e
es ed o hei in i o an ibac e ial ac i i ies agains ou di e en bac e ial s ains. The M-1 molecule shows high
an ibac e ial ac i i y.[39]
Figu e 23 S uc u e o M-1 molecule
Table 1 Di e en subs i u ions on benzimidazole mannich bases
R1
R2
R3
R4
R5
X
-
H
H
H
H
N
3c
H
H
COOH
H
H
C
3d
OH
H
SO3H
H
H
C
3e
OCF3
H
H
H
H
C
3
Emadi A (2020) The minimum inhibi o y concen a ion (MIC) and minimum ungicidal concen a ion (MFC) o he
syn hesized schi bases we e in es iga ed agains se en ungi s ains ( wo Fusa ium and i e Aspe gillus) and ou een
pa hogenic human bac e ia and compa ed o he nalidixic acid. Compounds 3.c– exhibi ed a s onge e ec on he g am-
nega i e bac e ia Klebsiella pneumonia and Esche ichia coli.[40]
Figu e 24 Gene al s uc u e o compounds 3c-
Işık A e al., (2024) se e al new benzimidazole- hiadiazole hyb ids we e syn hesized and hei an imic obial ac i i ies
we e e alua ed agains h ee ungal s ains and eigh pa hogenic bac e ial s ains. Azi h omycin, o iconazole, and
luconazole we e used as s anda d d ugs. Compounds 5 and 5h, wi h MIC alue o 3.90 μg/mL, displayed good
an i ungal ac i i y agains Candida albicans. In addi ion, compounds 5a, 5b, 5 , and 5h p e iously exhibi ed
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400
an imic obial ac i i y agains E. aecalis (ATCC 2942), wi h a MIC alue o 3.90 μg/mL. F om he HOMO–LUMO analysis,
compound 5h (wi h a educed ΔE = 3.417 eV) is chemically mo e ac i e compa ed o o he molecules, as can be in e ed
om he esul s displaying he maximum an ibac e ial and an i ungal ac i i y.[41]
Figu e 25 S uc u e o compound 5h
Bansal S e al., (2024) a ious new 2-(1H-benzimidazole-2-yl) phenyl)-2-(subs i u ed benzylidene) hyd azine
compounds we e syn hesized and p epa ed. The pha macological p ope ies o he p epa ed compounds, such as hei
an i ungal and an ibac e ial ac i i ies, we e s udied in i o. Compound 4i was ound o be mos ac i e agains S. au eus
and B. sub ilis, while 4d and 4e we e ound o be mos ac i e agains P. aeu igenosa and E. coli. De i a i e 4c possesses
s ong ac i i y agains C. albicans and A. nige .[42]
Figu e 26 Gene al s uc u e o compounds 4c,4d,4e & 4i
Oduselu GO e al., (2025) syn hesized amidoxime-based benzimidazole and benzimidamide sca olds and es ed hei
an imic obial ac i i y bo h in i o and in silico. Be e binding ene gies we e u nished by compounds 2b and 2a and
hese we e −8.0 kcal mol−1 o 2VF5 and −11.7 kcal mol−1 o 1IYL, espec i ely. Fo Candida albicans, compound had
a zone o inhibi ion and minimum inhibi o y concen a ion o 42 mm and 1.90 mg mL−1, while S. mu ans, compound
had 40 mm and 3.90 mg mL−1, acco ding o he esul s o an ibac e ial ac i i y.[43]
Figu e 27 S uc u es o compounds 2b, 2a
3. Conclusion
Benzimidazole, due o i s s uc u al simila i y o pu ine bases, can in e ac wi h mic obial DNA and enzymes, he eby
dis up ing essen ial cellula p ocesses and making i a aluable nucleus o d ug design. I s de i a i es exhibi b oad
an imic obial po en ial, wi h an ibac e ial ac i i y epo ed agains bo h G am-posi i e and G am-nega i e bac e ia,
pa icula ly when subs i u ed wi h halogens, ni o g oups, o he e oa yl moie ies ha enhance hei abili y o in e e e
wi h DNA syn hesis, p o ein exp ession, o cell wall o ma ion. In addi ion, benzimidazoles display signi ican an i ungal
Code R
4c 2-OCH
3
4d 3-Cl
4e 3-OCH
3
4i 4-NO
2
