Antileishmanial activity of MDL 28170, a potent calpain inhibitor
Antileishmanial activity of MDL 28170, a potent calpain inhibitor
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DOI：
10.1016/j.ijantimicag.2006.03.021
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发表时间：
2006-08-01
影响因子：
10.8
通讯作者：
Branquinha, Marta H.
中科院分区：
文献类型：
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作者：
d'Avila-Levy, Claudia M.;Marinho, Fernanda A.;Branquinha, Marta H.
几种钙蛋白酶抑制剂正在开发中，其中一些是对抗重要人类病原体的有用药物。因此，我们研究了强效钙蛋白酶抑制剂MDL 28170对亚马逊利什曼原虫生长的影响。48 h后，抑制剂表现出剂量依赖性的抗利什曼原虫活性，50%致死剂量（LD50）为23.3 μ m。抑制剂促进细胞改变，如寄生虫变得短而圆。Western blotting检测到一个在80kda迁移的calpain样蛋白。此外，鞭毛虫的细胞表面还发现了钙蛋白酶样分子。这些结果为利用钙蛋白酶抑制剂治疗寄生虫感染提供了新的体外见解，并将该肽酶家族添加到开发更有效和特异性的抗锥虫抑制剂的潜在靶点列表中。(c) 2006 Elsevier B.V.和国际化学疗法学会。版权所有。
Several calpain inhibitors are under development and some are useful agents against important human pathogens., We therefore investigated the effect of MDL 28170, a potent calpain inhibitor, on the growth of Leishmania amazonensis. After 48 h of treatment, the inhibitor exhibited a dose-dependent antileishmanial activity, with a 50% lethal dose (LD50) of 23.3 mu M. The inhibitor promoted cellular alterations, such as the parasites becoming short and round. A calpain-like protein migrating at 80 kDa was identified by Western blotting. In addition, the calpain-like molecules were identified on the cell surface of the flagellate. These results add new in vitro insights into the exploitation of calpain inhibitors in treating parasitic infections and add this family of peptidases to the list of potential targets for development of more potent and specific inhibitors against trypanosomatids. (c) 2006 Elsevier B.V. and the International Society of Chemotherapy. All rights reserved.