Department of Chemistry, Université de Montréal, Station Centre-Ville, C.P. 6128, Montreal, QC H3C 3J7, Canada.
Schools of Biology and Chemistry, Biomedical Sciences Research Complex, University of St. Andrews, St. Andrews, Fife, Scotland KY16 9ST, UK.
Bioorg Med Chem Lett. 2024 Sep 15;110:129883. doi: 10.1016/j.bmcl.2024.129883. Epub 2024 Jul 14.
The protozoan parasites Trypanosoma brucei, Trypanosoma cruzi and Leishmania spp. are responsible for continued propagation of neglected tropical diseases such as African sleeping sickness, Chagas disease and leishmaniasis respectively. Following a report that captopril targets Leishmania donovani dipeptidyl carboxypeptidase, a series of simple proline amides and captopril analogues were synthesized and found to exhibit 1-2 μM in vitro inhibition and selectivity against Trypanosoma brucei, Trypanosoma cruzi and Leishmania spp. The results were corroborated with computational docking studies. Arguably, the synthetic proline amides represent the structurally simplest examples of in vitro pan antiprotozoal compounds.
原生动物寄生虫布氏锥虫、克氏锥虫和利什曼原虫分别导致非洲昏睡病、恰加斯病和利什曼病等被忽视热带病的持续传播。有报道称卡托普利可靶向利什曼原虫二肽基羧肽酶，随后合成了一系列简单的脯氨酸酰胺和卡托普利类似物，并发现它们对布氏锥虫、克氏锥虫和利什曼原虫均具有 1-2 μM 的体外抑制作用和选择性。计算对接研究结果证实了这一点。可以说，这些合成的脯氨酸酰胺代表了体外泛抗原生动物化合物的结构最简单的例子。
