Pharmacological Evaluation and Biological Screening of Novel Benzimidazole Derivatives As Antimicrobial Agents.

Abstract

A series of sixteen novel benzimidazole derivatives was synthesized via nucleophilic substitution of 2-chloromethyl-1H-benzimidazole precursors and comprehensively characterized by melting point determination, IR, NMR, MS, and elemental analysis. The compounds were evaluated in vitro for antimicrobial activity against Staphylococcus aureus, Escherichia coli, Bacillus cereus, Candida albicans, and Aspergillus fumigatus using a standardized broth-microdilution assay. Select derivatives (notably 3m and 3p) exhibited minimum inhibitory concentrations as low as 1 µg/mL, outperforming reference agents. Antiquorum-sensing potential was assessed via violacein inhibition in Chromobacteriumviolaceum, where compound 3p achieved the largest QS-inhibitory zone. Cytotoxicity against human cancer cell lines (HepG2, HCT-116, MCF-7) and normal lung fibroblasts (W138) was determined by MTT assay, revealing sub-5 µM IC₅₀ values and selectivity indices averaging above 6. DNA-binding affinity studies further corroborated an intercalative mode of action for the most active molecules. The convergence of potent antimicrobial, antivirulence, and anticancer activities particularly in compound 3p underscores their promise as multifunctional therapeutic leads.