核素掺入研究布替萘芬对真菌麦角甾醇生物合成的影响  

The effect of butenafine on ergosterol biosynthesis in fungi by measuring incorporation of nuclide

作　　者：王科兵[1] 张璐璐[2] 程滨[3] 刘洪涛[4] 曹永兵[2] 姜远英[2] 

机构地区：[1]解放军第169医院药械科,湖南衡阳421001 [2]第二军医大学药学院,上海200433 [3]第二军医大学科研部,上海200433 [4]首都医科大学附属北京口腔医院药剂科,北京100050

出　　处：《药学实践杂志》2013年第5期359-361,365,共4页Journal of Pharmaceutical Practice

基　　金：国家自然科学基金(81273556)

摘　　要：目的研究抗真菌药物布替萘芬对真菌麦角甾醇生物合成的影响。方法通过真菌活细胞[1-^(14)C]乙酸钠掺入和离细胞液[2-^(14)C]甲羟戊酸掺入实验,考察布替萘芬对真菌麦角甾醇生物合成的影响。结果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,两种方法测得布替萘芬对真菌细胞麦角甾醇生物合成的IC_(50)分别为136.19 nmol/L和203.15 nmol/L。结论布替萘芬为角鲨烯环氧化酶抑制剂,核素掺入法能定量考察布替萘芬对角鲨烯环氧化酶的抑制活性,且效果优于薄层色谱扫描法。Objective To study the effect of butenaflne on ergosterol biosynthesis in fungi by measuring incorporation of nu- clide. Methods The inhibitory effect of butenafine on ergosterol biosynthesis in whole-cell fungi was studied by measuring the incor- poration of [ 1-14C] acetate into nonsaponifiable lipids（NSLs） , while the effect in cell-free extracts was studied by measuring the in- corporation of [ 2-14C ] mevalonate into NSLs. Results The synthesis of ergosterol in fungi was significantly decreased after butenafine treatment, whereas the level of squalene was increased. The IC50 value of butenafine on ergosterol biosynthesis was 136.19 nmol/L in whole-cell study and 203.15 nmol/L in cell-free study. Conclusion The method to measure the incorporation of [ 1-14C ] acetate and [ 2-14C ] mevalonate into NSLs of fungi, which could indicate the level of squalene, might be widely used to study the mechanism of in- hibitor of squalene epoxidase.

关 键 词：布替萘芬 麦角甾醇 角鲨烯环氧化酶 核素掺入 液体闪烁计数 

分 类 号：R978.5[医药卫生—药品]