Synthesis and Evaluation of New Antimalarial Phenylurenyl Chalcone Derivatives

Abstract

Phenylurenyl chalcone derivatives have been synthesized and tested as inhibitors of in vitro development of a chloroquine-resistant strain of Plasmodium falciparum, activity of the cysteine protease falcipain-2, in vitro globin hydrolysis, β-hematin formation, and murine Plasmodium berghei malaria. The most active antimalarial compound was 1-[3‘-N-(N‘-phenylurenyl)phenyl]-3(3,4,5-trimethoxyphenyl)-2-propen-1-one 49, with an IC₅₀ of 1.76 μM for inhibition of P. falciparum development. Results suggest that chalcones exert their antimalarial activity via multiple mechanisms.