Prediction of Antimicrobial Activities of Benzimidazole Derivatives Containing an Amide Bond Through Molecular Docking Analysis

Gram-positive and Gram-negative bacterial infections are one of the most important causes of illness and death worldwide. Although antibiotics are the primary treatment for these infections, the increase in the number of drug-resistant bacteria has posed a serious threat to public health in a global scale. Benzimidazole derivatives possess a distinctive chemical structure that exhibits a wide range of biological and therapeutic properties, including notable antimicrobial activity. In this study, we performed molecular docking analyses of four benzimidazole derivatives targeting dihydrofolate reductase, DNA gyrase, and 7,8-dihydro-6-hydroxymethylpterin-pyrophosphokinase enzymes from C. albicans, Escherichia coli, and Staphylococcus aureus. The relative binding free energy of the protein-ligand complexes were also calculated by the molecular mechanics-generalized born surface area (MM-GBSA) method. The relative binding free energy of the protein–ligand complexes were also calculated by the molecular mechanics-generalized born surface area (MM-GBSA) method. All tested compounds showed good potential as dihydrofolate reductase inhibitors and antifungal activity against Candida albicans. Notably, the compound 9A demonstrates the highest antimicrobial activity. Furthermore, all compounds are anticipated to exhibit greater activity against DNA gyrase in both E. coli and S. aureus compared to their respective cognate ligands. Compounds 9A/9B caused higher antimicrobial activity than compounds 10A/10B.