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 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.
León
Caritza
C
Laboratorio de Síntesis Orgánica, Facultad de Farmacia, Universidad Central de Venezuela, Caracas 1051, Venezuela.
Rodrigues
Juan
J
Gamboa de Domínguez
Neira
N
Charris
Jaime
J
Gut
Jiri
J
Rosenthal
Philip J
PJ
Domínguez
José N
JN
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*
D000962:Antimalarials; D013453:Sulfonylurea Compounds; D002738:Chloroquine