Synthesis of chlorovinyl sulfones as structural analogs of chalcones and their antiplasmodial activities.
The synthesis of novel chlorovinyl sulfone-like chalcone derivatives and their antimalarial activity against cultured Plasmodium falciparum parasites, hemozoin formation, hemoglobin hydrolysis and murine malaria model are described. Compounds were prepared via Claisen-Schmidt condensation from available chloromethylphenyl sulfones with substituted aldehydes. Antiplasmodial IC(50) activity of these compounds ranged between 0.025 and 10 microM, those that blocked P. falciparum development at low micro molar concentrations were tested in a murine Plasmodium berghei model, and these compounds delayed the progression of malaria but did not eradicate infections. Much effort and attention are needed for discovery and development of new and less toxic antimalarial drugs.
Dominguez
Jose N
JN
Laboratorio de Síntesis Orgánica, Facultad de Farmacia, Universidad Central de Venezuela, Caracas 1051, Venezuela. jdomingu@cantv.net
Leon
Caritza
C
Rodrigues
Juan
J
Gamboa de Dominguez
Neira
N
Gut
Jiri
J
Rosenthal
Philip J
PJ
D000818:Animals; D000962:Antimalarials / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D002599:Chalcone / Q000031:analogs & derivatives*; D006420:Hemeproteins / Q000378:metabolism; D006454:Hemoglobins / Q000378:metabolism; D006801:Humans; D006868:Hydrolysis / Q000187:drug effects; D008288:Malaria / Q000188:drug therapy; D051379:Mice; D010962:Plasmodium berghei / Q000187:drug effects; D010963:Plasmodium falciparum / Q000187:drug effects*; D013450:Sulfones / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use
D000962:Antimalarials; D006420:Hemeproteins; D006454:Hemoglobins; D013450:Sulfones; C020753:hemozoin; D002599:Chalcone