布替萘芬体外抗真菌活性及对真菌麦角甾醇合成的影响

目的研究抗真菌药物布替萘芬的体外抗真菌活性和对真菌麦角甾醇生物合成的影响。方法以氟康唑和酮康唑为对照,分别用微量液基稀释法和薄层色谱扫描法研究布替萘芬的体外抗真菌活性和对真菌麦角甾醇生物合成的影响。结果布替萘芬对念珠菌属的MIC大于16μg/ml,对新生隐球菌的MIC为1～8μg/ml,对浅部真菌的MIC小于4μg/ml。布替萘芬能使真菌中麦角甾醇的合成减少,而增加角鲨烯的含量,其含量变化与布替萘芬均呈剂量依赖性。结论布替萘芬的体外抗真菌活性优于氟康唑,与酮康唑作用相当,其对部分浅部真菌的抗菌活性优于酮康唑。布替萘芬为角鲨烯环氧化酶抑制剂,其作用靶酶与氮唑类抗真菌药不同,用薄层色谱扫描法能考察其对角鲨烯环氧化酶的抑制活性。

In vitro antifungal activity of butenafine and its effect on ergosterol biosynthesis in fungi

Objective To study in vitro antifungal activity of butenafine and its effect on ergosterol biosynthesis in fungi. Methods MICs of butenafine for 43 isolates of fungi were tested with the broth ~microdilution testing, and its effect on ergosterol biosynthesis in fungi was determined by the method of thin-layer chromatography (TLC). Results When the biological activity of butenafine was tested against 43 ~isolates of fungi, a wide range of sensitivity was recorded. Butenafine showed lower activities against all yeast-like fungi except for Cryptococcus neoformans compared with fluconazole and ketoconazole. Against the filamentous fungus, even including Aspergillus fumigatus, butenafine was found to have a stronger activity than fluconazole and ketoconazole. Butenafine was found to inhibit ergosterol biosynthesis and caused the concentration of squalene increased with a dose-dependent manner in fungi. Conclusion These results provide a rational basis for the clinical use of butenafine in superficial mycoses and show that butenafine inhibits the fungal ~enzyme squalene epoxidase, thereby blocking the biosynthesis of ergosterol. The method of TLC can be used to study the activity and mechanism of new antifungal agents.