Background: The benzimidazole ring is an important pharmacophore in modern
drug discovery. Mannich reaction is one of the versatile reaction widely used in organic
synthesis. Mannich base derivatives play an important role in medical field with diverse
Objective: A series of N-(benzimidazol-1-ylmethyl)-4-chlorobenzamide derivatives (3a-
3m) were synthesized and evaluated for anti-inflammatory and antimicrobial potential.
Method: Mannich reaction was used to synthesize N-(benzimidazol-1-ylmethyl)-4-
chlorobenzamide analogues. The structures of novel target compounds were elucidated by
spectral and analytical techniques and screened for in vivo anti-inflammatory activity and
ulcerogenic activity. In addition, the prepared derivatives were also evaluated for in vitro
antimicrobial activity against gram negative, gram positive and fungal strains. Further, in
silico studies were carried out to define the interaction of the title compounds with COX-2
enzyme and microbial protein.
Results: The results revealed that out of thirteen molecules, compound 3a (containing
chloromethyl substituent at 2-position of benzimidazole) showed significant antiinflammatory
effect at a dose of 100 mg/kg p.o. and the experimental data was statistically
significant at p≤0.05 level. Diclofenac sodium was taken as standard drug for antiinflammatory
activity. Furthermore, derivative 3e (containing 2-chlorophenyl moiety at 2-
position of benzimidazole scaffold) was found to be the most effective antimicrobial compound
among the synthesized derivatives. Ciprofloxacin and clotrimazole were used as reference
antimicrobial agents. Results from in vivo and in vitro studies of synthesized analogues
were found to be in good correlation with in silico study.
Conclusion: These results designate that N-(Benzimidazol-1-ylmethyl)-4-chlorobenzamide
analogues, substituted with halogen functionality, could be used as potential lead for designing
more potent anti-inflammatory and antimicrobial agents.