DL-α-二氟甲基鸟氨酸对敏感及耐药布氏布氏锥虫的评估

Evaluation of DL-alpha-difluoromethylornithine against susceptible and drug-resistant Trypanosoma brucei brucei.

作者信息

Zweygarth E, Kaminsky R

机构信息

Kenya Trypanosomiasis Research Institute (KETRI), Kikuyu.

出版信息

Acta Trop. 1991 Jan;48(3):223-32. doi: 10.1016/0001-706x(91)90050-t.

DOI:10.1016/0001-706x(91)90050-t

PMID:1671624

Abstract

The antitrypanosomal activity of the ornithine decarboxylase inhibitor DL-alpha-difluoromethylornithine (DFMO, eflornithine) was tested in ten stocks and one clone of the hemoflagellate Trypanosoma brucei brucei in an in vitro system. They showed varying levels of susceptibility to DFMO, their IC50 (the concentration which inhibited growth by 50%) values ranging from 81-691 microM. Differences in DFMO susceptibility were also demonstrated in mice. Combinations of melarsonyl potassium (mel W; trimelarsan) and DFMO showed an additive effect in vitro in a mel W-susceptible and a mel W-resistant stock, but an antagonistic effect in a mel W- and DFMO-susceptible clone. Combinations of suramin and DFMO showed an antagonistic effect in vitro in a suramin-susceptible clone, but a potentiation in a suramin-resistant stock.

摘要

在体外系统中，对鸟氨酸脱羧酶抑制剂DL-α-二氟甲基鸟氨酸（DFMO，依氟鸟氨酸）的抗锥虫活性进行了测试，受试对象为10个布氏布氏锥虫血鞭毛虫株系和1个克隆。它们对DFMO的敏感性各不相同，其半数抑制浓度（IC50，即抑制生长50%的浓度）值在81 - 691微摩尔之间。在小鼠体内也证实了对DFMO敏感性的差异。在一个对美拉胂钾（美拉胂醇W；三巯密胺）敏感和一个对美拉胂钾耐药的株系中，美拉胂钾（美拉胂醇W）与DFMO的组合在体外显示出相加作用，但在一个对美拉胂钾和DFMO均敏感的克隆中显示出拮抗作用。在一个对苏拉明敏感的克隆中，苏拉明与DFMO的组合在体外显示出拮抗作用，但在一个对苏拉明耐药的株系中显示出增效作用。