Synthesis, DFT Calculations, Studies, and Antimicrobial Evaluation of Benzimidazole-Thiadiazole Derivatives.

In this study, a series of new benzimidazole-thiadiazole hybrids were synthesized, and the synthesized compounds were screened for their antimicrobial activities against eight species of pathogenic bacteria and three fungal species. Azithromycin, voriconazole, and fluconazole were used as reference drugs in the mtt assay. Among them, compounds and showed potent antifungal activity against with a MIC of 3.90 μg/mL. Further, the results of the antimicrobial assay for compounds , , , and proved to be potent against (ATCC 2942) on the basis of an acceptable MIC value of 3.90 μg/mL. The cytotoxic effects of compounds that are effective as a result of their antimicrobial activity on healthy mouse fibroblast cells (L929) were evaluated. According to HOMO-LUMO analysis, compound (with the lower Δ = 3.417 eV) is chemically more reactive than the other molecules, which is compatible with the highest antibacterial and antifungal activity results. A molecular docking study was performed to understand their binding modes within the sterol 14-α demethylase active site and to interpret their promising fungal inhibitory activities. Molecular dynamics (MD) simulations of the most potent compounds and were found to be quite stable in the active site of the 14-α demethylase (5TZ1) protein.