Identification of novel antifungal agents: antimicrobial evaluation, SAR, ADME-Tox and molecular docking studies of a series of imidazole derivatives.

Thirty-four imidazole-based compounds synthesized by one-pot catalytic method were evaluated for their antifungal and antibacterial activities against several fungal and bacterial strains. None of the compounds had antibacterial activity. Interestingly, compounds , , , and displayed a strong antifungal activity against all the tested fungal species, while compounds , , , , and showed a moderate antifungal activity. To better understand the biological activity of the most active compounds ADME-Tox and molecular docking studies were carried out. Interestingly, compounds , , , , and showed excellent bioavailability. In addition, compounds , and , exhibited good toxicity profiles. Docking studies of the two most active compounds (IC of 95 ± 7.07 μM) and (IC of 235 ± 7.07 μM) suggested that they might act by inhibiting the fungal lanosterol 14α-demethylase. Therefore, these novel antifungal agents merit further characterization for the development of new antifungal therapeutics.