EFFECTS OF KETOCONAZOLE ON STEROL BIOSYNTHESIS BY TRYPANOSOMA-CRUZI EPIMASTIGOTES
EFFECTS OF KETOCONAZOLE ON STEROL BIOSYNTHESIS BY TRYPANOSOMA-CRUZI EPIMASTIGOTES
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DOI：
10.1016/0006-291x(86)90410-9
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发表时间：
1986-05-14
影响因子：
3.1
通讯作者：
HOLZ, GG
中科院分区：
文献类型：
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作者：
BEACH, DH;GOAD, LJ;HOLZ, GG
抗真菌剂酮康唑可抑制克氏锥虫上鞭毛体在肝浸液-胰蛋白胨-血清培养基中的繁殖。放射性同位素、色谱和质谱方法证明，有效的药物浓度还在 C-15 去甲基化阶段阻断了寄生虫的真菌型甾醇的生物合成。巧合的是，4,4,14.α.-三甲基甾醇，24-亚甲基二氢羊毛甾醇，积累并取代了细胞中多达四分之三的游离甾醇含量。援引真菌研究的先例表明，酮康唑对克氏锥虫的细胞毒性是由于 24-亚甲基二氢羊毛甾醇无法发挥正常表鞭毛体甾醇的膜脂胆功能的结果。
Reproduction of Trypanosoma cruzi epimastigotes in a liver infusion-tryptose-serum medium was inhibited by the antimycotic agent ketoconazole. Effective drug concentrations also blocked the biosynthesis of the parasite''s fungal-type sterols at the stage of C-15 demethylation, as demonstrated by radioisotopic, chromatographic and mass spectrometric methods. Coincidently, a 4,4,14.alpha.-trimethyl sterol, 24-methylenedihydrolanosterol, accumulated and came to replace as much as three fourths of the free sterol content of the cells. Precedents from studies with fungiare are invoked to suggest that the cytotoxicity of ketoconazole for T. cruzi is a consequence of the inability of 24-methylenedihydrolanosterol to perform the membrane lipid bilary functions of the normal epimastigote sterols.