布氏锥虫介体型半胱氨酸蛋白酶抑制剂的设计与评估。
Design and evaluation of Trypanosoma brucei metacaspase inhibitors.
机构信息
Laboratory of Medicinal Chemistry, University of Antwerp, Antwerp, Belgium.
出版信息
Bioorg Med Chem Lett. 2010 Mar 15;20(6):2001-6. doi: 10.1016/j.bmcl.2010.01.099. Epub 2010 Jan 25.
Abstract
Metacaspase (MCA) is an important enzyme in Trypanosoma brucei, absent from humans and differing significantly from the orthologous human caspases. Therefore MCA constitutes a new attractive drug target for antiparasitic chemotherapeutics, which needs further characterization to support the discovery of innovative drug candidates. A first series of inhibitors has been prepared on the basis of known substrate specificity and the predicted catalytic mechanism of the enzyme. In this Letter we present the first inhibitors of TbMCA2 with low micromolar enzymatic and antiparasitic activity in vitro combined with low cytotoxicity.
摘要
介体型半胱天冬酶（MCA）是布氏锥虫中的一种重要酶，在人体内不存在，与同源的人半胱天冬酶有显著差异。因此，MCA 构成了抗寄生虫化学疗法的一个新的有吸引力的药物靶标，需要进一步进行特征描述以支持创新药物候选物的发现。基于已知的底物特异性和酶的预测催化机制，已经制备了第一系列抑制剂。在这封信中，我们首次报道了具有低微摩尔酶活性和抗寄生虫活性的 TbMCA2 的抑制剂，同时具有低细胞毒性。
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