Anti-Candida Activity of YH-1715R,a New Triazole Derivative
Anti-Candida Activity of YH-1715R,a New Triazole Derivative
박강식(연세대학교); HEUI-IL KANG(Yonsei University,); JONG WOOK LEE(Yonsei University,); YOUNG-KI PAIK(Yuhan Research Center)
14권 4호, 693~697쪽
초록
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 thestructural modification of fluconazole, was found to exhibitpotent anti-Candida activity against a wide variety ofCandida albicans (C. albicans) (MIC: 0.4- 12.5 mg/l). Toinvestigate the mode of action of YH-1715R, its effect onergosterol biosynthesis in cell-free extracts and whole cells ofC. albicans was examined. The inhibitory activity of YH-1715R was approximately ten-fold higher than that offluconazole. To determine the primary action mechanism ofYH-1715R, its inhibitory activity against lanosterol 14α-demethylase (14α-DM), a major target for azole, wasmeasured using gas-liquid chromatography. YH-1715R andfluconazole were found to inhibit 14α-DM with an IC50 of0.015 μM and 0.018 μM, respectively, plus the mode ofinhibition of YH-1715R and fluconozole was noncompetitivewith a Ki of 0.0533 μM and 0.0975 μM.
Abstract
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 thestructural modification of fluconazole, was found to exhibitpotent anti-Candida activity against a wide variety ofCandida albicans (C. albicans) (MIC: 0.4- 12.5 mg/l). Toinvestigate the mode of action of YH-1715R, its effect onergosterol biosynthesis in cell-free extracts and whole cells ofC. albicans was examined. The inhibitory activity of YH-1715R was approximately ten-fold higher than that offluconazole. To determine the primary action mechanism ofYH-1715R, its inhibitory activity against lanosterol 14α-demethylase (14α-DM), a major target for azole, wasmeasured using gas-liquid chromatography. YH-1715R andfluconazole were found to inhibit 14α-DM with an IC50 of0.015 μM and 0.018 μM, respectively, plus the mode ofinhibition of YH-1715R and fluconozole was noncompetitivewith a Ki of 0.0533 μM and 0.0975 μM.
- 발행기관:
- 한국미생물·생명공학회
- 분류:
- 생물학