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

Abstract

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 <b>1</b>, <b>2</b>, <b>3</b>, <b>10</b> and <b>15</b> displayed a strong antifungal activity against all the tested fungal species, while compounds <b>5</b>, <b>7</b>, <b>9</b>, <b>11</b>, <b>21</b> and <b>27</b> 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 <b>1</b>, <b>2</b>, <b>3</b>, <b>7</b>, <b>10</b> and <b>15</b> showed excellent bioavailability. In addition, compounds <b>1</b>, <b>2</b> and <b>3</b>, exhibited good toxicity profiles. Docking studies of the two most active compounds <b>2</b> (IC₅₀ of 95 ± 7.07 μM) and <b>10</b> (IC₅₀ 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.