Berman J D, Holz G G, Beach D H
Mol Biochem Parasitol. 1984 May;12(1):1-13. doi: 10.1016/0166-6851(84)90039-2.
Ketoconazole, a clinically effective antimycotic agent active in vitro against the amastigote stage of Leishmania mexicana Walter Reed 227 in human monocyte-derived macrophages, was found to inhibit growth and impair sterol biosynthesis of the cultured promastigote stage by approx. 50% at a concentration of approx. 10(-8)M. Sterol biosynthesis was interfered with at the level of the removal of the 14 alpha-methyl group of lanosterol, as judged by changes in the distribution of [2-14C]mevalonate radioactivity among desmethyl sterol and methyl sterol thin-layer chromatography fractions, by the loss of 4-desmethyl sterols (mainly 5-dehydroepisterol), and by the accumulation of 14 alpha-methyl sterols. The growth inhibition and sterol changes were evident in promastigotes cultured in a cholesterol-rich medium and in a cholesterol-poor medium, even though promastigotes incorporated cholesterol. The mechanism of action of ketoconazole against promastigotes may be that postulated for Candida albicans: interference with membrane permeability secondary to loss of desmethyl sterols and accumulation of 14 alpha-methyl sterols.
酮康唑是一种临床有效的抗真菌剂，在体外对人单核细胞衍生巨噬细胞中的墨西哥利什曼原虫沃尔特·里德227株的无鞭毛体阶段具有活性。研究发现，酮康唑在浓度约为10(-8)M时，可抑制培养的前鞭毛体阶段的生长并损害其甾醇生物合成，抑制率约为50%。根据[2-14C]甲羟戊酸放射性在去甲基甾醇和甲基甾醇薄层色谱组分中的分布变化、4-去甲基甾醇（主要是5-脱氢表甾醇）的损失以及14α-甲基甾醇的积累判断，甾醇生物合成在羊毛甾醇14α-甲基去除水平受到干扰。即使前鞭毛体摄取了胆固醇，在富含胆固醇的培养基和缺乏胆固醇的培养基中培养的前鞭毛体中，生长抑制和甾醇变化也是明显的。酮康唑对前鞭毛体的作用机制可能与白色念珠菌的作用机制相同：继发于去甲基甾醇的损失和14α-甲基甾醇的积累而干扰膜通透性。
