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评价三种新型氮甾体化合物对刚地弓形虫的作用。

Evaluation of three novel azasterols against Toxoplasma gondii.

机构信息

Laboratório de Ultraestrutura Celular Herth, Meyer, Instituto de Biofísica Carlos Chagas Filho, UFRJ, CCS, Bloco G, Av. Carlo, Chagas Filho, Cidade Universitária, Ilha do Fundão, 21941-902, Rio de Janeiro, RJ, Brazil.

出版信息

Vet Parasitol. 2011 Apr 19;177(1-2):157-61. doi: 10.1016/j.vetpar.2010.11.034. Epub 2010 Dec 1.

Abstract

Previous studies from our group have demonstrated the high susceptibility of Toxoplasma gondii tachyzoites to the sterol analogues 22,26-azasterol and 24,25-(R,S)-epiminolanosterol. In this work we present data on testing in vitro three novel azasterols as potential agents for the treatment of toxoplasmosis. The three compounds inhibited parasite growth at micromolar concentrations, in a dose-dependent manner. Electron microscopy analysis of intracellular tachyzoites after treatment with the most effective compound showed drastic mitochondrion swelling associated with the appearance of an electron-lucent matrix and disrupted cristae. Parasite lysis also took place. The appearance of electron dense cytoplasmic structures similar to amylopectin granules distributed throughout the parasite suggests that azasterols might be inducing differentiation of those tachyzoites which were not lysed to the bradyzoite stage.

摘要

先前本课题组的研究已经表明,速殖子对甾体类似物 22,26-氮杂胆固醇和 24,25-(R,S)-表绵马甾醇极为敏感。在这项工作中,我们提供了三种新型氮杂胆固醇作为潜在抗弓形虫药物进行体外检测的数据。这三种化合物以剂量依赖的方式在微摩尔浓度下抑制寄生虫生长。用最有效的化合物处理后,对胞内速殖子进行电子显微镜分析显示,线粒体严重肿胀,出现电子透明基质和嵴结构破坏。寄生虫也发生裂解。出现类似于分布在整个寄生虫中的支链淀粉颗粒的电子致密细胞质结构,这表明氮杂胆固醇可能诱导未裂解的速殖子向缓殖子阶段分化。

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