Discovery of trypanocidal thiosemicarbazone inhibitors of rhodesain and TbcatB
Discovery of trypanocidal thiosemicarbazone inhibitors of rhodesain and TbcatB
复制标题
DOI：
10.1016/j.bmcl.2008.03.083
复制
发表时间：
2008-05-01
影响因子：
2.7
通讯作者：
Guy, R. Kiplin
中科院分区：
文献类型：
--
作者：
Mallari, Jeremy P.;Shelat, Anang;Guy, R. Kiplin
人类非洲锥虫病 (HAT) 是由原生动物寄生虫布氏锥虫引起的。布氏锥虫的半胱氨酸蛋白酶已被证明对寄生虫复制至关重要，并且代表了治疗干预的一个有吸引力的点。在此，我们描述了一系列缩氨基硫脲的合成及其针对锥虫组织蛋白酶 TbcatB 和罗得赛因以及人组织蛋白酶 L 和 B 的活性。这些化合物的活性针对培养的布氏锥虫进行了测定，并用一组四种哺乳动物细胞系评估了特异性。 (c) 2008 Elsevier Ltd. 保留所有权利。
Human African trypanosomiasis ( HAT) is caused by the protozoan parasite Trypanosoma brucei. The cysteine proteases of T. brucei have been shown to be crucial for parasite replication and represent an attractive point for therapeutic intervention. Herein we describe the synthesis of a series of thiosemicarbazones and their activity against the trypanosomal cathepsins TbcatB and rhodesain, as well as human cathepsins L and B. The activity of these compounds was determined against cultured T. brucei, and specificity was assessed with a panel of four mammalian cell lines. (c) 2008 Elsevier Ltd. All rights reserved.