Design, synthesis and investigation of new imidazole derivatives with biological activities and antifungal effects

Fungal infections are important types of infection that annually cause the death of many people around the world. Therefore, new antifungal agents that are more effective and less toxic are constantly needed. In this study, new imidazole derivatives were synthesized and their antifungal activities were investigated. Compound <b>5d</b> showed antifungal activity against <i>Candida albicans</i>, <i>Candida parapsilosis</i> and <i>Candida krusei</i> with a minimum inhibitory concentration (MIC₅₀) of 0.98 µg/mL. While compound <b>5e</b> showed antifungal effects against <i>C. albicans</i> and <i>C. parapsilosis</i> with MIC₅₀ of 0.98 µg/mL, it displayed potent antifungal activity against <i>C. krusei</i> with MIC₅₀ of 1.96 µg/mL. Compound <b>5h</b> exhibited antifungal activity against <i>C. albicans</i> and <i>C. parapsilosis</i> with MIC₅₀ of 1.96 and 0.98 µg/mL, respectively. It is known that azole group antifungals inhibit ergosterol biosynthesis by inhibiting the 14α-demethylase enzyme. For this reason, in the present study <i>in silico</i> studies were performed on 14α-demethylase enzyme crystal (PDB ID: 1EA1). Molecular docking and dynamics studies were conducted to examine the binding modes of the active compounds (<b>5d</b>, <b>5e</b> and <b>5h</b>). The results of the <i>in silico</i> studies agreed with the biological activity results.