Abstract

DESIGN, SYNTHESIS AND ANTIFUNGAL EVALUATION OF NOVEL TRIAZOLE DERIVATIVES AS FLUCONAZOLE ANALOGUE

*Ashvini H. Pagare, Sachin N. Kapse, Rani S. Kankate, Dr. Anwar R. Shaikh

ABSTRACT

A series of 1-(5-(4-phenyl)-1,3,4-oxadiazol-2-yl)-2-(2,4-difluorophenyl)-3-(1H-1,2,4-triazol-1-yl)propan-2-ols compounds were synthesized and evaluated for their antifungal activities in- vitro. As most 6A-6E compounds exhibited good in-vitro antifungal activity, this finding supported our attention that attachment of fluoro and chloro group to the phenyl ring increases the antifungal activity of the compound. On the other hand, replacing the chloro and fluoro group with nitro group almost eliminated the antifungal activity, which was demonstrated by the low antifungal activity of compounds 6G-6I. Combining the results from this study and from previous research, we propose that the optimal strategy to maximize the antifungal activity of compound was to condense substituted 1,3,4-oxadiazoles as the replacement to 1,2,4-triazole ring of fluconazole. The substituted group on the 1,3,4-oxadiazole ring could also contribute significantly to antifungal activity. The structure-activity relationships of the synthesized compounds were discussed, and the docking model of the target compounds with fungal lanosterol 14α-demethylase (CYP51) was analyzed.

Keywords: Triazole derivatives, Fluconazole analogues, Lanosterol 14-?-demethylase (CYP51), Antifungal activity and docking interactions.