Synthesis and evaluation of sulfonylurea derivatives as novel antimalarials

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 IC50 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.

A series of sulfonylurea derivatives were synthesized to evaluate their activity as antimalarials, in vitro and in vivo. The results of this study suggest quite potent antimalarials. R: Cl, Me; R′: a – 2,4-diOMeC6H3; b – 4-FC6H4; c – 3,4-OCH2OC6H3; d – 4-ClC6H4; e – 2,4-diClC6H3; f – 2,4-diFC6H3; g – 3,4,5-triOMeC6H2; h – C6H5; i – 4-MeC6H4; j – 4-OMeC6H4; k – C5H4N; l – b-C10H7; m – 3-C9H5NCl; n – 6,7-diOMe-3-C9H5NCl.Figure optionsDownload as PowerPoint slide