Haughan P A, Chance M L, Goad L J
Department of Biochemistry, University of Liverpool, U.K.
Exp Parasitol. 1993 Sep;77(2):147-54. doi: 10.1006/expr.1993.1071.
The S-adenosylmethionine analogue sinefungin was tested in vitro against promastigotes of various strains of Leishmania. The IC50 values for the Leishmania mexicana, Leishmania major, and Leishmania donovani strains used were of the order of 10 ng/ml but the Leishmania amazonensis strain tested was more resistant to the drug, the IC50 value being 6 micrograms/ml. Sterol profiles, in which 24-alkyl (C28) sterols predominated, were relatively unaffected by sinefungin. Incorporation of label derived from either [methyl-2H3]methionine or [methyl-14C]methionine into sterols was not appreciably affected by treatment at a growth-inhibiting concentration of sinefungin. It was concluded that sinefungin had only a limited effect on sterol production at the 24-transmethylation step and it is unlikely that this is the primary cause of cell death.
对S-腺苷甲硫氨酸类似物杀稻瘟菌素进行了体外测试，以检测其对各种利什曼原虫菌株前鞭毛体的作用。所用的墨西哥利什曼原虫、硕大利什曼原虫和杜氏利什曼原虫菌株的半数抑制浓度（IC50）值约为10纳克/毫升，但所测试的亚马逊利什曼原虫菌株对该药物更具抗性，IC50值为6微克/毫升。以24-烷基（C28）甾醇为主的甾醇谱相对不受杀稻瘟菌素的影响。在杀稻瘟菌素的生长抑制浓度下进行处理，源自[甲基-2H3]甲硫氨酸或[甲基-14C]甲硫氨酸的标记掺入甾醇中并未受到明显影响。得出的结论是，杀稻瘟菌素在24-甲基转移步骤对甾醇产生的影响有限，并且这不太可能是细胞死亡的主要原因。
