Anti-Candida activity of YH-1715R, a new triazole derivative

YH-1715R, (2R,3R)-2-(2,4-difluorophenyl)-3-(3-methoxy-1,2,4-isothiazol- 3-yl-thio)-1-(1H-1,2,4-triazol-1-yl)-2-butanol, a new triazole derivative obtained by the structural modification of fluconazole, was found to exhibit potent anti-Candida activity against a wide variety of Candida albicans (C. albicans) (MIC: 0.4-12.5 mg/l). To investigate the mode of action of YH-1715R, its effect on ergosterol biosynthesis in cell-free extracts and whole cells of C. albicans was examined. The inhibitory activity of YH-1715R was approximately ten-fold higher than that of fluconazole. To determine the primary action mechanism of YH-1715R, its inhibitory activity against lanosterol 14α-demethylase (14α -DM), a major target for azole, was measured using gas-liquid chromatography. YH-1715R and fluconazole were found to inhibit 14α-DM with an IC₅₀ of 0.015 μM and 0.018 μM, respectively, plus the mode of inhibition of YH-1715R and fluconozole was noncompetitive with a K_i of 0.0533 μM and 0.0975 μM.