Design and synthesis of some novel 1 2 disubstituted benzimidazole analogues for potential anti microbial and anti inflammatory activity

Abstract

Designed, synthesized and evaluated a sequence of novel benzimidazol-1-yl-1-phenylpropanone (Series-1) and benzimidazol-1-yl-1-(4-chlorophenyl) propan-1-one (Series-2) hybrids for in vitro antimicrobial and antioxidant potential and for in vivo anti-inflammatory action. Various bacterial strains (Escherichia coli, Pseudomonas aeruginosa, Bacillus subtilis, Staphylococcus aureus) and fungal strains (Candida albicans and Aspergillus niger) were utilized for the course of analysis. Computational methodology was carried out for designing of the target molecules via AutoDock Vina software. Cyclooxygenase-2 (PDB id: 4COX), DNA gyrase B (PDB id:4KFG) and clotrimazole complexed with cytochrome P45046A1 (PDB id:3MDV) were the chosen targets for the whole study. Derivatives were prepared via Mannich and Schiff base reaction after molecular docking studies. Twenty seven novel analogues were selected for synthesis and biological evaluation. Characterization of synthesized compounds was done by various analytical techniques. Amid the integrated fifteen derivatives of Series-1, 6g was found to acquire excellent antibacterial activity followed by 6c. Derivatives 6h and 6l declared good to moderate antibacterial results and 6f and 6j displayed significant antifungal action. In addition, amongst twelve derivatives from Series-2, 6k and 6j were splendid molecules for antibacterial action whereas analogues 6k and 6a were found to be more dynamic against both the fungal strains. For the whole study ciprofloxacin and clotrimazole were used as reference drugs. Antioxidant study was also performed by DPPH antiradical assay and Ascorbic acid was used as standard drug for the analysis. From the in-silico studies, twenty hybrids having dock score higher than internal ligand, Indomethacin (-7.7 kcal/mol) from both the series were selected for anti-inflammatory activity. Further, out of twenty hybrids, based on anti-inflammatory results (plt0.05), ten compounds were selected from both the series for analgesic potential. Results disclosed