Design, synthesis and trypanocidal activity of lead compounds based on inhibitors of parasite glycolysis
Design, synthesis and trypanocidal activity of lead compounds based on inhibitors of parasite glycolysis
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DOI：
10.1016/j.bmc.2008.03.045
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发表时间：
2008-05-01
影响因子：
3.5
通讯作者：
Turner, Nicholas J.
中科院分区：
文献类型：
--
作者：
Nowicki, Matthew W.;Tulloch, Lindsay B.;Turner, Nicholas J.
糖酵解途径被认为是对抗寄生原生动物锥虫属和利什曼原虫属的潜在药物靶标。我们报告了布氏锥虫磷酸果糖激酶（PFK）和墨西哥利什曼原虫丙酮酸激酶（PyK）的抑制剂的设计和合成。逐步库合成和抑制剂设计从一个合理的起点确定呋喃糖糖氨基酰胺作为一种新型的抑制剂，这两种酶的IC（50）值分别为23 μ M和26 μ M对PFK和PyK。杀锥虫活性也显示出在低微摩尔范围内的效力，并证实这些抑制剂作为有希望的候选物用于开发抗锥虫药物的设计。(c)2008爱思唯尔有限公司保留所有权利。
The glycolytic pathway has been considered a potential drug target against the parasitic protozoan species of Trypanosoma and Leishmania. We report the design and the synthesis of inhibitors targeted against Trypanosoma brucei phosphofructokinase (PFK) and Leishmania mexicana pyruvate kinase (PyK). Stepwise library synthesis and inhibitor design from a rational starting point identified furanose sugar amino amides as a novel class of inhibitors for both enzymes with IC(50) values of 23 mu M and 26 mu M against PFK and PyK, respectively. Trypanocidal activity also showed potency in the low micromolar range and confirms these inhibitors as promising candidates for the development towards the design of anti-trypanosomal drugs. (c) 2008 Elsevier Ltd. All rights reserved.