Discovery and Structure-Activity Relationships of Quinazolinone-2-carboxamide Derivatives as Novel Orally Efficacious Antimalarials

A phenotypic high-throughput screen allowed discovery of quinazolinone-2-carboxamide derivatives as a novel antimalarial scaffold. Structure-activity relationship studies led to identification of a potent inhibitor 19f, 95-fold more potent than the original hit compound, active against laboratory-resistant strains of malaria. Profiling of 19f suggested a fast in vitro killing profile. In vivo activity in a murine model of human malaria in a dose-dependent manner constitutes a concomitant benefit.

Automated summary

A novel antimalarial scaffold was discovered through a phenotypic high-throughput screen, with a potent inhibitor 19f identified as 95-fold more potent than the original hit compound. Profiling of 19f showed a fast in vitro killing profile, and its in vivo activity in a murine model of human malaria was dose-dependent, providing a concomitant benefit.