文献类型：期刊文献

英文题名：Synthesis, Design, and Structure-Activity Relationship of the Pyrimidone Derivatives as Novel Selective Inhibitors of Plasmodium falciparum Dihydroorotate Dehydrogenase

作者：Xu, Le[1];Li, Wenjie[1];Diao, Yanyan[1];Sun, Hongxia[1];Li, Honglin[1];Zhu, Lili[1];Zhou, Hongchang[2];Zhao, Zhenjiang[1]

机构：[1]East China Univ Sci & Technol, Sch Pharm, Shanghai Key Lab New Drug Design, Shanghai 200237, Peoples R China;[2]Huzhou Teachers Coll, Med Sch, Dept Microbiol, Huzhou 313000, Peoples R China

年份：2018

卷号：23

期号：6

外文期刊名：MOLECULES

收录：;WOS:【SCI-EXPANDED(收录号:WOS:000435875400016)】；

基金：This work was supported by the National Key Research and Development Program (Grant 2016YFA0502304), the National Natural Science Foundation of China (Grants 21372078 and 81302697), and the Fundamental Research Funds for the Central Universities.

语种：英文

外文关键词：P. falciparum; PfDHODH; pyrimidone; antimalarial agents

摘要：The inhibition of Plasmodium falciparum dihydroorotate dehydrogenase (PfDHODH) potentially represents a new treatment option for malaria, as P. falciparum relies entirely on a de novo pyrimidine biosynthetic pathway for survival. Herein, we report a series of pyrimidone derivatives as novel inhibitors of PfDHODH. The most potent compound, 26, showed high inhibition activity against PfDHODH (IC50 = 23 nM), with >400-fold species selectivity over human dihydroorotate dehydrogenase (hDHODH). The brand-new inhibitor scaffold targeting PfDHODH reported in this work may lead to the discovery of new antimalarial agents.