Trypanosomatidae Diseases: From the Current Therapy to the Efficacious Role of Trypanothione Reductase in Drug Discovery
Trypanosomatidae Diseases: From the Current Therapy to the Efficacious Role of Trypanothione Reductase in Drug Discovery
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DOI：
10.2174/0929867311320210005
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发表时间：
2013-07-01
影响因子：
4.1
通讯作者：
Carvalho, I.
中科院分区：
文献类型：
--
作者：
Bernardes, L. S. C.;Zani, C. L.;Carvalho, I.
据世界卫生组织（世卫组织）称，锥虫病和利什曼病是被忽视的热带疾病中最具挑战性的。利什曼原虫属和克氏锥虫之间的比较研究已经进行，目的是找到一种广谱抗原虫剂对这两种寄生虫。在潜在的分子靶标中，锥硫酮还原酶（TR）被认为是理想的酶，因为它参与在锥虫科中观察到的独特的基于巯基的代谢，并且是用于寻找抗锥虫科药物的经验证的靶标。在这篇综述中，我们打算描述目前可用的治疗锥虫科疾病，并强调锥硫酮还原酶的重要方面作为一个目标，寻找新的和选择性的抑制剂，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-氨基羰基和，α，β-不饱和羰基衍生物。
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 beta-aminocarbonyl and, alpha,beta-unsaturated carbonyl derivatives.