Departamento de Ciências Farmacêuticas, Universidade Federal de Santa Catarina, Campus Universitário, Florianópolis, SC, Brazil, CEP 88040-970.
Curr Med Chem. 2013;20(21):2673-96. doi: 10.2174/0929867311320210005.
According to World Health Organization (WHO), trypanosomiasis and leishmaniasis are the most challenging among the neglected tropical diseases. Comparative studies between Leishmania spp and Trypanosoma cruzi have been conducted aiming to find a broad spectrum antiprotozoal agent acting against both parasites. Among the potential molecular target, Trypanothione reductase (TR) is considered an ideal enzyme since it is involved in the unique thiol-based metabolism observed in the Trypanosomatidae family and is a validated target for the search of antitrypanosomatidae drugs. In this review we intend to describe the currently available therapy to treat trypanosomatidae diseases and to highlight important aspects of trypanothione reductase as a target for the search of new and selective inhibitors, such as tricyclic, diphenylsulfide, bicyclic and heterocyclic, polyamine, natural product, N-oxide and nitroheterocyclic, aryl β-aminocarbonyl and α,β-unsaturated carbonyl derivatives.
根据世界卫生组织（WHO）的说法，锥虫病和利什曼病是被忽视的热带病中最具挑战性的疾病。已经进行了利什曼原虫属和克氏锥虫之间的比较研究，旨在寻找一种广谱抗原生动物剂，对两种寄生虫都有作用。在潜在的分子靶标中，三肽还原酶（TR）被认为是一种理想的酶，因为它参与了在锥虫科家族中观察到的独特的基于硫醇的代谢，并且是寻找抗锥虫药物的验证靶标。在这篇综述中，我们旨在描述目前可用于治疗锥虫病的治疗方法，并强调三肽还原酶作为寻找新的和选择性抑制剂的目标的重要方面，如三环、二苯硫醚、双环和杂环、多胺、天然产物、N-氧化物和硝基杂环、芳基β-氨基甲酰基和α、β-不饱和羰基衍生物。
