Synthesis, DFT, and Molecular Docking Studies of Substituted Benzimidazole Scaffolds as Potential Antimicrobial and Antitubercular Agents

ABSTRACT The rise in antibiotic resistance has become a global health challenge as many of the existing drugs are increasingly ineffective in combating infectious diseases. The benzimidazole hybrids have emerged as new class of antimicrobial agents and as a result there is considerable attention in the design and synthesis of new benzimidazole derivatives. This study describes the synthesis of benzimidazole hybrids and their characterization by FTIR, NMR ( 1 H and 13 C) and mass spectral data. The compounds were screened for antimicrobial potential against the ESKAPE Panel, NTMs, and M. tuberculosis H37Rv27294. Among the tested compounds, 2,4‐dibromo‐6‐(5‐nitro‐1H‐benzo[d]imidazol‐2‐yl)phenol ( 3c ) demonstrated significant potential to inhibit E. faecalis and S. aureus with an MIC values of 1.0 and 0.5 µg/mL, respectively. Compound (3c ) also exhibited immense potential against M. tuberculosis H37Rv27294 with the MIC, 8.0 µg/mL Molecular docking studies on S. aureus tyrosyl‐tRNA synthetase protein, which is essential for bacterial survival, revealed that among all the compounds screened, compound ( 3c ) possesses better affinity with a binding energy of −9.85 kcal/mol. Further, investigation of 3c targeting KasA (β‐ketoacyl‐acyl carrier protein), a crucial enzyme in the mycobacterial FAS‐II pathway, showed a binding energy of −7.1 kcal/mol suggesting 3c could be explore as a promising lead molecule.