Mattock N M, Peters W
Ann Trop Med Parasitol. 1975 Sep;69(3):359-71.
A variety of compounds used in the treatment of parasitic or bacterial infections in man, including leishmaniasis itself, were examined for their activity against three lines of Leishmania in tissue culture. The organisms used were L. mexicana mexicana, L. tropical major and L. donovani; they were grown in dog sarcoma and hamster peritoneal exudate cell lines. Leishmanicidal activity was observed in a number of compounds currently in clinical use for the treatment of one or other form of leishmaniasis. Cycloguanil, nifurtimox, amphotericin B and monomycin were effective but pentamidine showed poor activity. In each case marked differences were observed in the level of response in the different parasite lines. Organic antimonials were most active when anmastigotes were exposed to them prior to entry of the parasites into host cells. This suggests that such compounds may exert an effect on amastigotes during their brief extracellular transit from one host cell to another in vivo. A number of antimalarials showed good to moderate leishmanicidal action, particularly against L. mexicana and L.t. major. Several schistosomicidal agents also possessed leishmanicidal properties. The commonly used broad spectrum antibiotics showed little if any activity. In discusssion a comparison is drawn between data published on the action of some of these drugs against L.t. major in mice and our observations with the same strain and L. mexicana in tissue culture. A remarkably good agreement is found for most of the compounds examined. General agreement is also noted between these data and reports of clinical trials although it is not possible to draw too many conclusions because of the failure in most clinical studies to make an accurate identification of the causative Leishmania. It is concluded that, although the tissue culture model is not to be considered as ideal and can probably be improved, data obtained by its use do bear relevance to the action compounds in vivo, and the model may be use in the screening of drugs for leishmanicidal activity.
对多种用于治疗人类寄生虫或细菌感染（包括利什曼病本身）的化合物，检测了它们在组织培养中对三株利什曼原虫的活性。所用的生物体为墨西哥利什曼原虫、热带利什曼原虫和杜氏利什曼原虫；它们在犬肉瘤和仓鼠腹腔渗出细胞系中培养。在目前临床上用于治疗一种或另一种形式利什曼病的许多化合物中观察到了杀利什曼原虫活性。环氯胍、硝呋莫司、两性霉素B和莫能霉素有效，但喷他脒活性较差。在每种情况下，不同寄生虫株的反应水平存在显著差异。当无鞭毛体在进入宿主细胞之前暴露于有机锑化合物时，有机锑化合物最为活跃。这表明此类化合物可能在无鞭毛体在体内从一个宿主细胞短暂转运至另一个宿主细胞的细胞外过程中对其产生影响。一些抗疟药表现出良好至中等的杀利什曼原虫作用，尤其是对墨西哥利什曼原虫和热带利什曼原虫。几种杀血吸虫剂也具有杀利什曼原虫特性。常用的广谱抗生素几乎没有活性。在讨论中，对已发表的关于其中一些药物对小鼠体内热带利什曼原虫作用的数据与我们在组织培养中对同一菌株和墨西哥利什曼原虫的观察结果进行了比较。在所检测的大多数化合物中发现了非常好的一致性。这些数据与临床试验报告之间也存在总体一致性，尽管由于大多数临床研究未能准确鉴定致病的利什曼原虫，无法得出太多结论。得出的结论是，虽然组织培养模型并非理想模型，可能还有改进空间，但通过使用该模型获得的数据确实与化合物在体内的作用相关，并且该模型可用于筛选具有杀利什曼原虫活性的药物
