Synthesis, evaluation and molecular docking studies of Schiff base derived benzimidazole-2-thiols as an antimicrobial agent

Background and Aim: In recent years an increasing frequency and severity of antimicrobial resistance to different antimicrobial agents, demands new remedies for treatment of infections. Benzimidazole nitrogen containing heterocyclic compound, is important scaffold and gained significant attraction towards antibacterial activities. Therefore, the aim of present work was to synthesize a series of 2-((1H-benzo[d]imidazol-2-yl)thio)-N'-benzylideneacetohydrazides (4-13) and evaluated their in-vitro antimicrobial activity against selected pathogenic bacterial and fungal strains. Methods: The synthesis of the intermediate and target compounds was performed by standard procedure. Synthesized compounds were screened for antimicrobial activity by tube dilution method. Molecular docking study of synthesized derivatives was also performed to find out their interaction with the target site of topoisomerase enzyme using Autodock Vina software. Results: Compounds 7-9 and 11 with electron withdrawing groups at phenyl ring showed good efficacy against tested strains. Further, docking results revealed that benzimidazole part of compound 11 buried in the D chain, showed the hydrophilic interaction at ARG1122 amino acid residue, whereas another part (Schiff base) showed similar hydrophilic interaction with B chain at ARG458 amino acid residue. Binding affinity of most potent compound 11 (-9.8 Kcal/mol) was comparable to standard drug ciprofloxicin (-10 Kcal/mol). Conclusion: Compound 11 with meta-NO2 substituted phenyl ring showed the highest potency as well as binding affinity with target site among synthesized compounds. These observations show that hybrid of benzimidazole and Schiff base with electron withdrawing groups could be an important lead for further development of antimicrobial agent against resistant microbial strains.