title: 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 1.2microM 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.
authors.affiliation: Laboratorio de Síntesis Orgánica, Facultad de Farmacia, Universidad Central de Venezuela, Caracas 1051, Venezuela.
authors.forename: Caritza
authors.initials: C
authors.lastname: León
authors.forename: Juan
authors.initials: J
authors.lastname: Rodrigues
authors.forename: Neira
authors.initials: N
authors.lastname: Gamboa de Domínguez
authors.forename: Jaime
authors.initials: J
authors.lastname: Charris
authors.forename: Jiri
authors.initials: J
authors.lastname: Gut
authors.forename: Philip J
authors.initials: PJ
authors.lastname: Rosenthal
authors.forename: José N
authors.initials: JN
authors.lastname: Domínguez
mesh_terms: D000818:Animals; D000962:Antimalarials / Q000138:chemical synthesis* / Q000494:pharmacology*; D002738:Chloroquine / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004351:Drug Resistance; D008288:Malaria / Q000188:drug therapy; D008297:Male; D051379:Mice; D008968:Molecular Conformation; D010962:Plasmodium berghei; D010963:Plasmodium falciparum / Q000187:drug effects; D013453:Sulfonylurea Compounds / Q000138:chemical synthesis* / Q000494:pharmacology*
chemical_list: D000962:Antimalarials; D013453:Sulfonylurea Compounds; D002738:Chloroquine