Synthesis, Molecular Docking, Dynamics, Quantum-Chemical Computation, and Antimicrobial Activity Studies of Some New Benzimidazole-Thiadiazole Hybrids.

In this study, some new compounds, which are 2-aminothiadiazole derivatives linked by a phenyl bridge to the 2-position of the benzimidazole ring, were designed and synthesized as antimicrobial agents. The structures of the compounds were elucidated by H and C NMR spectroscopy, high-resolution mass spectrometry, and elemental analysis. The antifungal activities of the synthesized compounds were tested on , , , and . Compound is more active against and than standard fluconazole and varicanazole. Compounds were also evaluated for their counteracting activity against Gram-positive , , , and and Gram-negative , , and . Compounds and had minimum inhibitory concentrations against close to that of the standard azithromycin. Molecular docking studies were performed against species' 14-α demethylase enzyme. was the most active compound against species, which gave the highest docking interaction energy. The stabilities of compounds and with CYP51 were tested using 100 ns molecular dynamics simulations. According to the theoretical ADME calculations, the profiles of the compounds are suitable in terms of limiting rules. HOMO-LUMO analysis showed that is chemically more reactive (represented with the lower Δ = 3.432 eV) than the other molecules, which is compatible with the highest antibacterial activity result.