Antimicrobial potential of 1H-benzo[d]imidazole scaffold: a review

Background Benzimidazole is a heterocyclic moiety whose derivatives are present in many of the bioactive compounds and posses diverse biological and clinical applications. Benzimidazole agents are the vital pharmacophore and privileged sub-structures in chemistry of medicine. They have received much interest in drug discovery because benzimidazoles exhibited enormous significance. So attempts have been made to create repository of molecules and evaluate them for prospective inherent activity. They are extremely effective both with respect to their inhibitory activity and favorable selectivity ratio. Conclusion Benzimidazole is most promising category of bioactive heterocyclic compound that exhibit a wide variety of biological activities in medicinal field. The present review only focus on antimicrobial activity of reported benzimidazole derivatives may serve as valuable source of information for researchers who wish to synthesize new molecules of benzimidazole nucleus which have immense potential to be investigated for newer therapeutic possibilities.


Antimicrobial activity
Ansari et al. synthesized 2-substituted-1H-benzimidazole derivatives by nucleophilic substitution reaction and evaluated their antimicrobial activity against selected microbial species. The compounds 1a, 1b, 1c and 1d showed good antibacterial activity as well as compound 1c showed good antifungal activity (Table 1, Fig. 2). SAR study inferred that at 2-position of oxadiazole ring increased side chain carbon atom number causes an enhanced the antimicrobial activity toward C. albicans, S. aureus and B. subtilis and also the para-substituted phenyl nucleus supported the activity [9].
Ansari et al. reported a series of 2-mercaptobenzimidazole derivatives and screened for its in vitro antimicrobial activity (using cup-plate agar diffusion method) against selected microbial species i.e. E. coli, B. subtilis, A. flavus, C. albicans and A. niger. Structure activity relationship studies revealed that compounds having o-Cl (2f and 2h), o-CH 3 (2g and 2i), -OH (2b, 2c and 2d) and p-NH 2 (2e) groups in phenyl ring as well as compound 2a without substitution displayed significant antibacterial potential which is comparable to the reference drugs ( Table 2, Fig. 2) [12].
Arjmand et al. synthesized novel Cu(II) complex benzimidazole derivative via condensation of 2-mercaptobenzimidazole with diethyloxalate and screened for their antimicrobial activity against bacterial (E. coli, S. aureus) and fungal (A. niger) species. Compound 3a exhibited highest activity against the bacterial as well inhibited the growth of fungal species (Table 3, Fig. 3) [13].
A novel series of benzimidazole derivatives was reported by Ayhan-Kilcigil et al. and evaluated for its antimicrobial potential against selected strains by the tube dilution technique. Compound, 4a showed significant antimicrobial potential against B. subtilis and P. aeruginosa with MIC values of 12.5 and 25 µg/mL, respectively which is comparable to ampicillin (MIC = 6.25 and 25 µg/ mL) as well 4a and 4b (Fig. 3) showed good antifungal activity with MIC values of 6.25 and 12.5 µg/mL (C.  Compounds, 5a, 5b and 5c (Fig. 3) showed good activity as compared to standard ciprofloxacin. Additionally, compounds 5a and 5c showed absolute bactericidal activity against tested strains within 24 h, whereas ciprofloxacin kill those bacteria in 48 h (Table 4) [15]. Barot Fig. 4) [17].
Goker et al. developed novel substituted benzimidazole carboxamidine molecules and assessed for their antibacterial activity by tube dilution method against selected microbes. Compounds 10a and 10b displayed significant antibacterial activity (Table 9, Fig. 4) as comparable to standard drugs (ampicillin and sultamicillin) [18].
Kalinowska-Lis et al. synthesized silver (I) complexes of benzimidazole and screened for their antimicrobial activity against S. epidermidis, S. aureus and C. albicans. In this series, compound 15a (Fig. 5) exhibited good antifungal but moderate antibacterial activity as compared to standard drugs AgNO 3 and silver sulfadiazine (AgSD) ( Table 13) [23].
Kankate et al. developed novel benzimidazole analogues and screened for their in vitro (tube dilution technique) and in vivo antifungal activity (kidney burden test) against C. albicans. Compound 16a (Fig. 5) exhibited superior in vitro antifungal activity with MIC value of 0.0075 µmol/mL as comparable to fluconazole while in vivo activity was significantly less (P < 0.001) [24].
Khalafi-Nezhad et al. synthesized some chloroaryloxyalkyl benzimidazole derivatives and screened for their in vitro antimicrobial activity against S. typhi and S. aureus using disk diffusion method. Compound 17a showed good antibacterial activity against the tested microbial species (Table 14    Kucukbay et al. synthesized new electron-rich olefins benzimidazole compounds and evaluation for their in vitro antimicrobial activity against the selected microbial species and compared to standard drug. Among the prepared compounds, 20a and 20b were found to be most effective against C. albicans and C. tropicalis (Table 17, Fig. 5) [28].  compounds (13a, 14a-14c, 15a, 16a, 17a, 18a, 19a-19b, 20a-20b) Kumar et al. developed a new series of substituted benzimidazole scaffolds and screened for its in vitro antibacterial potential against S. aureus and S. typhimurium and compared to cephalexin as standard. Compounds, 21a and 21b exhibited good antibacterial activity against S. typhimurium whereas showed pitiable activity against S. aureus (Table 18, Fig. 6) [29].
Kumar et al. reported a series of trisubstituted benzimidazole molecules and screened for its antimicrobial potential against F. tularensis LVS strain using Microplate Alamar Blue assay. Compounds, 22a and 22b (Fig. 6) exhibited promising antimicrobial activity with MIC values of 0.35 and 0.48 µg/mL [30].
Kerimov et al. developed new benzimidazole derivatives and evaluated for their antifungal activity against C. albicans and C. krusei by the agar diffusion method using fluconazole as standard. Among the synthesized compounds, compound 41a (Table 42 and Fig. 9) found to be most active against tested fungal species [49].
Si et al. synthesized a series of new benzimidazole scaffolds and evaluated for their antifungal activity against Botrytis cinerea and Sclerotinia sclerotiorum using thiabendazole and azoxystrobin as references. In this series, compound 42a exhibited excellent antifungal activity (Table 43 and Fig. 9) [50].
Tahlan et al. reported a class of novel benzimidazole Schiff base derivatives and screened for its antimicrobial potency against tested microbial strains by tube dilution method. Among the synthesized compounds, 43a   structures of compounds (27a-27e, 28a-28c, 29a-29b, 30a-30b, 31a and 43b were found to be most potent antifungal agents against A. niger and C. albicans (Table 44 and Fig. 9) [51]. Tahlan et al. reported a series of new benzimidazole Schiff base derivatives and evaluated for its antimicrobial potency against selected microbial species. In this series, compounds 44a and 44b showed significant antimicrobial activity towards tested bacterial and fungal strains (Table 45 and Fig. 9) [52].         (32a-32b, 33a-33d, 34a, 35a, 36a-36b, 37a-     Yadav et al. synthesized a series of novel benzimidazole derivatives and accessed for its antimicrobial activity against S. aureus, B. subtilis, E. coli, C. albicans and A. niger by serial dilution method using ciprofloxacin and fluconazole as standard drugs. From the synthesized derivatives, compounds 45a and 45b showed excellent antimicrobial activity against selected microorganisms (Tables 46, 47 and Fig. 9) [53].