Antibacterial, Antifungal and Molecular Docking Studies of N1‐Substituted 5‐Alkylsulfonyl Benzimidazole Derivatives

Abstract Infectious diseases pose a significant threat to global healthcare, especially with the rapid emergence of antimicrobial resistance and limited development of antimicrobials. Hence, the search for new and effective antimicrobial is paramount. Benzimidazole represents a unique, aromatic heterocycle with broad spectrum of biological applications. The present study aimed to evaluate the antibacterial and antifungal activities, and molecular docking studies of N1‐substituted 5‐alkylsulfonyl benzimidazole derivatives ( 23 – 36) synthesized in our previous work. The compounds were tested for their in vitro antimicrobial activity against diverse strains of Gram‐positive and Gram‐negative bacteria, and fungal species using the microdilution assay. In silico docking analysis of the most promising compounds was also investigated against DNA Gy r and DHFR targets to simulate the ligand‐receptor interaction. Compound 26, bearing cyclohexyl and 3,4‐difluorophenyl moieties at the N1 and C2 positions of the benzimidazole ring, respectively displayed the most potent antibacterial activity against E. faecalis (MIC = 12.5 µg/mL), and the most potent antifungal activity (MIC = 16 µg/mL) against Candida albicans and Candida parapsilosis . The molecular docking analysis provided useful insights into the interaction of the molecules with key amino acid residues. This compound provides useful lead for the development of novel antibacterial and antifungal agent against susceptible organisms.