Design, synthesis and antifungal evaluation of 1-(2-(2,4-difluorophenyl)-2-hydroxy-3-(1H-1,2,4-triazol-1-yl)propyl)-1H-1,2,4-triazol-5(4H)-one

Based on the structure of the active site of cytochrome P450 14α-demethylase (CYP51) and the conclusions of the structure-activity relationships of azole antifungals, a series of 1-(2-(2,4-difluoro-phenyl)-2-hydroxy-3-(1H-1,2,4-triazol-1-yl)propyl)-1H-1,2,4-triazol-5(4H)-one of fluconazole analogs was synthesized. All compounds were characterized by IR, HRMS, 1HNMR and 13C NMR spectroscopic analysis. Results of preliminary antifungal in vitro test using eight human pathogenic species showed that some compounds displayed comparable or even better antifungal activities than reference drug fluconazole and that compound 3i exhibited significant activity against Candida albicans being worthy of further optimization.

Graphical abstractA series of 1H-1,2,4-triazol-5(4H)-one derivatives were synthesized and tested for antifungal activities in vitro. The antifungal assay indicated some compounds exhibited activities against fungi tested to some extent.Figure optionsDownload full-size imageDownload as PowerPoint slideHighlights► A series of 1H-1,2,4-triazol-5(4H)-one analogs of fluconazole were designed and synthesized as novel antifungal agents. ► All compounds were evaluated by in vitro test against eight human pathogenic species. Preliminary results showed that some compounds displayed better antifungal activities than reference drug fluconazole against tested strains. ► Compound 3i exhibited significant activity against Candida albicans being worthy of further optimization.