Abstract

Designs, synthesis, structural elucidation and antimicrobial evaluation of various derivatives of 2-mercaptobenzimidazole as possible antimicrobial agents

Objective: Derivatives of 2-Mercaptobenzimidazole (2-MBI) are very significant heterocyclic compounds. 2-MBI and its derivatives have been showing different biological activates, the most significant activity exhibiting the antimicrobial activity. The aim of the project includes the synthesis of new derivatives of 2-MBI. Methods: Formation of 2-(Phenethylthio)-1H-benzo[d] imidazole (ZR-1) by alkylation, thioester S-(1H-benzo[d]imidazol-2-yl) O-ethyl carbonothioate (ZRJ2), S-(1H-benzo[d]imidazol-2-yl) O-isobutyl carbonothioate (ZR-4), and S-(1H-benzo[d] imidazol-2-yl) O-methyl carbonothioate (ZR-8), the reaction involves thio acetic derivative 2-((1H-benzo[d]imidazol2-yl) thio) acetic acid (ZR-3) with oxalyl chloride to generate acyl derivatives to this added cyclic amines to yield compounds, amid derivatives 2-((1H-benzo[d]imidazol-2-yl) thio)-1-(2, 6-dimethylpiperidin-1-yl) ethan-1-one (ZR-5), 2-((1H-benzo[d]imidazol-2-yl) thio)-1-(pyrrolidin-1-yl) ethan-1-one (ZR-6), and 2-((1H-benzo[d]imidazol2-yl) thio)-1-(4-methylpiperazin-1-yl) ethan-1-one (ZR-7). Results: Structure of newly synthesized compounds have been verified through FT-IR, DSC, Elemental analysis, 1H-NMR, 13C-NMR, and Molecular docking, it indicates one of these compound (ZR-5) has great affinity (-8.70) than our stander (trimethoprim -7.91Kcal/ mol. into DHFR). An antimicrobial activity was evaluated by agar diffusion methods and broth dilution test against Staphylococcus aureus (ATCC 6538), Escherichia coli (ATCC 8739), Pseudomonas aeruginosa (ATCC 9027), Bacillus subtilis (ATCC 6633) and Candida albicans (ATCC 10231). The Minimum Inhibitory Concentrations (MIC) and the Minimum Bactericidal Concentration (MBC) were determined and compared with ciprofloxacin (85.51%), trimethoprim and fluconazole (99.9%) as standard positive control drugs, Conclusion: Compound (ZR-8) showed excellent antifungal activity and good antibacterial activity compared to ciprofloxacin and trimethoprim. The results promoted the interest to do more structural modifications to enhance the antimicrobial activity and their antimicrobial selectivity

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