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The inhibition of Plasmodium falciparum dihydroorotate dehydrogenase ( Pf DHODH) 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 Pf DHODH. The most potent compound, 26 , showed high inhibition activity against Pf DHODH (IC 50 = 23 nM), with &gt;400-fold species selectivity over human dihydroorotate dehydrogenase ( h DHODH). The brand-new inhibitor scaffold targeting Pf DHODH reported in this work may lead to the discovery of new antimalarial agents.

molecules/molecules online/molecules annual

Synthesis, Design, and Structure–Activity Relationship of the Pyrimidone Derivatives as Novel Selective Inhibitors of Plasmodium falciparum Dihydroorotate Dehydrogenase