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.

Graphical abstractA 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 full-size imageDownload as PowerPoint slide