Evaluation of Jatropha isabelli natural products and their synthetic analogs as potential antimalarial therapeutic agents
Evaluation of Jatropha isabelli natural products and their synthetic analogs as potential antimalarial therapeutic agents
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DOI：
10.1016/j.ejmech.2013.04.030
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发表时间：
2013-07-01
影响因子：
6.7
通讯作者：
Rivas, Fatima
中科院分区：
文献类型：
--
作者：
Hadi, Victor;Hotard, Megan;Rivas, Fatima
疟疾等原生动物疾病是一个主要的世界卫生问题。为了寻找新的潜在的治疗线索，我们筛选了一个天然产物库，发现麻疯树（jatrophone）对恶性疟原虫307和K1菌株具有显著的活性。合成了一个聚焦的麻风细胞-支架文库，以评价麻风细胞的作用方式并鉴定更多选择性的类似物。该化合物库中化合物25和32对菌株3D7和K1具有微摩尔EC50值，为抗疟疾提供了一种新的分子支架。我们的报告描述了一种有效的衍生化方法，用于评估麻疯酮类似物的结构活性关系，以寻找潜在的新的抗疟疾药物。Elsevier Masson SAS出版。
Protozoal diseases such as malaria are a leading world health concern. We screened a library of fractionated natural products to identify new potential therapeutic leads and discovered that jatrophone (a product of Jatropha isabelli) exerts significant activity against Plasmodium falciparum strains 307 and K1. A focused jatrophone-scaffold library was synthesized to evaluate jatrophone's mode of action and identify more selective analogs. Compounds 25 and 32 of this natural product inspired compound library exhibited micromolar EC50 values against strains 3D7 and K1, thus providing a new antimalarial molecular scaffold. Our report describes an efficient derivatization approach used to evaluate the structure activity relationship of jatrophone analogs in search of potential new antimalarial agents. Published by Elsevier Masson SAS.