发现一种基于喹啉的苯砜衍生物作为抗锥虫剂。
Discovery of a quinoline-based phenyl sulfone derivative as an antitrypanosomal agent.
作者信息
Zhang Huaisheng, Collins Jasmine, Nyamwihura Rogers, Ware Shelbi, Kaiser Marcel, Ogungbe Ifedayo Victor
机构信息
Department of Chemistry, Jackson State University, Jackson, MS 39217, USA.
Department of Medical Parasitology & Infection Biology, Swiss Tropical and Public Health Institute, 4051 Basel, Switzerland; University of Basel, Petersplatz 1, 4003 Basel, Switzerland.
出版信息
Bioorg Med Chem Lett. 2018 May 15;28(9):1647-1651. doi: 10.1016/j.bmcl.2018.03.039. Epub 2018 Mar 24.
A series of natural products-based phenyl sulfone derivative and their property-based analogues were investigated as potential growth inhibitors of Trypanosoma brucei. Trypanosoma brucei is a kinetoplastid protozoan parasite that causes trypanosomiasis. In this work, we found that nopol- and quinoline-based phenyl sulfone derivative were the most active and selective for T. brucei, and they were not reactive towards the active thiol of T. brucei's cysteine protease rhodesain. A thiol reactive variant of the quinoline-based phenyl sulfone was subsequently investigated and found to be a moderate inhibitor of rhodesain. The quinoline-based compound that is not reactive towards rhodesain can serve a template for phenotypic-based lead discovery while its thiol-active congener can serve as template for structure-based investigation of new antitrypanosomal agents.
研究了一系列基于天然产物的苯砜衍生物及其基于性质的类似物作为布氏锥虫潜在生长抑制剂的情况。布氏锥虫是一种导致锥虫病的动质体原生动物寄生虫。在这项工作中，我们发现基于诺卜醇和喹啉的苯砜衍生物对布氏锥虫最具活性和选择性，并且它们对布氏锥虫半胱氨酸蛋白酶罗德西亚蛋白酶的活性硫醇没有反应性。随后研究了基于喹啉的苯砜的硫醇反应变体，发现它是罗德西亚蛋白酶的中度抑制剂。对罗德西亚蛋白酶无反应性的基于喹啉的化合物可作为基于表型的先导发现模板，而其硫醇活性类似物可作为基于结构的新型抗锥虫药物研究模板。
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