European Research Centre for Drug Discovery and Development (NatSynDrugs), University of Siena, Via A. Moro, 53100 Siena, Italy.
Bioorg Med Chem Lett. 2012 Aug 15;22(16):5317-21. doi: 10.1016/j.bmcl.2012.06.023. Epub 2012 Jun 23.
Plasmodium falciparum subtilisin-like protease 1 (PfSUB1) is a serine protease that plays key roles in the egress of the parasite from red blood cells and in preparing the released merozoites for the subsequent invasion of new erythrocytes. The development of potent and selective PfSUB1 inhibitors could pave the way to the discovery of potential antimalarial drugs endowed with an innovative mode of action and consequently able to overcome the current problems of resistance to established chemotherapies. Through the screening of a proprietary library of compounds against PfSUB1, we identified hydrazone 2 as a hit compound. Here we report a preliminary investigation of the structure-activity relationships for a class of PfSUB1 inhibitors related to our identified hit.
恶性疟原虫丝氨酸蛋白酶 1（PfSUB1）是一种丝氨酸蛋白酶，在寄生虫从红细胞中逸出以及为随后侵入新的红细胞准备释放的裂殖子方面发挥关键作用。开发有效和选择性的 PfSUB1 抑制剂可以为发现具有创新作用模式的潜在抗疟药物铺平道路，从而能够克服当前对现有化疗药物的耐药性问题。通过对 PfSUB1 的专有化合物库进行筛选，我们确定了腙 2 作为一个命中化合物。在这里，我们报告了对与我们鉴定的命中化合物相关的一类 PfSUB1 抑制剂的结构-活性关系的初步研究。
