Design, synthesis and antifungal activity of novel triazole derivatives containing substituted 1,2,3-triazole-piperdine side chains

•A series of novel antifungal triazoles with substituted triazole-piperidine side chains were designed and synthesized.•The target compounds showed good antifungal activity toward a wide range of pathogenic fungi.•Compound 8v was a highly potent fungal inhibitor.

Due to increasing incidence of invasive fungal infections and severe drug resistance to triazole antifungal agents, a series of novel antifungal triazoles with substituted triazole-piperidine side chains were designed and synthesized. Most of the target compounds showed good inhibitory activity against a variety of clinically important fungal pathogens. In particular, compounds 8t and 8v were highly active against Candida albicans and Cryptococcus neoformans with MIC values in the range of 0.125 μg/mL to 0.0125 μg/mL. They represent promising leads for the development of new generation of triazole antifungal agents. Molecular docking studies revealed that the target compounds interacted with CACYP51 mainly through hydrophobic and Van der Waals interactions.

Graphical abstractA series of novel antifungal triazoles with substituted triazole-piperidine side chains were designed and synthesized. Most of the target compounds showed good inhibitory activity against a variety of clinically important fungal pathogens.Figure optionsDownload full-size imageDownload as PowerPoint slide