Trypanosoma dionisii as an experimental model to study anti-Trypanosoma cruzi drugs: A comparative analysis with benznidazole, posaconazole and amiodarone

Barrias Es, Borges Tr, W. Desouza
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Abstract

Chagas disease is a public health problem in Latin America and its treatment is based on the use of benznidazole or nifurtimox compounds. Both present problems such as resistance, ineffi ciency in chronic infection and cytotoxic effects. New compounds such as posaconazole and amiodarone have been tested against T. cruzi and shown to be effective. In addition, new molecules have been synthesized and tested against T. cruzi. Because this protozoan is highly pathogenic, even with a number of cases of accidental laboratory infections, few laboratories located outside Latin America are authorized to work with its infective developmental stages. On the other hand, Trypanosoma dionisii is a non-pathogenic protozoan phylogenetically related to T. cruzi and that shares similar strategies to complete its life cycle in mammalian cells in vitro. Here, we describe a comparative analysis of the sensitivity of both parasites to benznidazole, posoconazole and amiodarone. We also analyzed the morphological effects of these compounds on both Trypanosoma species using electron microscopy. Our results show that T. dionisii is more sensitive to the compounds tested than T. cruzi. They also support a previous suggestion that it may constitute an excellent model for large scale screening of compounds against T. cruzi. Research Article
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以酒锥虫为实验模型研究抗克氏锥虫药物:与苯并硝唑、泊沙康唑和胺碘酮的比较分析
恰加斯病是拉丁美洲的一个公共卫生问题,其治疗基于使用苯并硝唑或硝呋替莫化合物。两者都存在耐药性、慢性感染无效和细胞毒性作用等问题。泊沙康唑和胺碘酮等新化合物已经对克氏锥虫进行了测试,并显示出有效的效果。此外,已经合成了新的分子并对克氏锥虫进行了测试。由于这种原生动物具有高致病性,即使有一些偶然的实验室感染病例,拉丁美洲以外的实验室很少被授权从事其感染发育阶段的工作。另一方面,在系统发育上与克氏锥虫相关的非致病性原生动物,在体外哺乳动物细胞中具有相似的完成其生命周期的策略。在这里,我们描述了两种寄生虫对苯并硝唑,泊康唑和胺碘酮敏感性的比较分析。我们还用电子显微镜分析了这些化合物对两种锥虫的形态学影响。结果表明,酒毒T. dionisii比克氏T. cruzi更敏感。他们还支持了先前的一个建议,即它可能构成一个极好的模型,用于大规模筛选抗克氏锥虫的化合物。研究文章
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