Synthesis and evaluation of sulfonylurea derivatives as novel antimalarials

Abstract

We have synthesized a series of sulfonylureas and have tested their antimalarial activities, including inhibition of in vitro development of a chloroquine-resistant strain of Plasmodium falciparum, in vitro hemoglobin hydrolysis, hemozoin formation, and development of Plasmodium berghei in murine malaria. The most active antimalarial compound was ( E)-1-[4′-(3-(2,4-difluorophenyl)acryloyl)phenyl]-3-tosylurea ( 22) with an IC 50 of 1.2 μM against cultured P. falciparum parasites. Biological results suggest a fairly potent antimalarial activity for this derivative, but also imply that its activity may arise from an unknown mechanism. Indeed, these compounds may act against malaria parasites through multiple mechanisms.