Synthesis and antifungal evaluation of new azole derivatives containing 1,2,3-triazole

RSC Med Chem. 2024 Oct 29. doi: 10.1039/d4md00724g. Online ahead of print.

Abstract

Invasive fungal infections caused by C. albicans are becoming increasingly serious and there is an urgent need for exploring new antifungal drugs. In the present work, a series of new azole derivatives containing a 1,2,3-triazole moiety have been prepared, and in vitro antifungal activity have been evaluated. The results revealed that most compounds showed excellent antifungal activity against C. albicans SC5314 and drug-resistant SC5314-FR. In particular, compounds 4h, 4j, 4l, 4s and 4w exhibited better antifungal activity than FLC. The preliminary mechanism study indicated that 4s could damage the integrity of the cell structure, increase the permeability of the cell membrane, and cause the leakage of cell contents of C. albicans. The molecular docking study indicated that 4s showed an obvious binding site with the target CYP51 (PDB ID: 5TL8). Therefore, 4s could be considered as a new antifungal agent targeting CYP51 for further study.