Antimalarial activity of new gossypol derivatives.
Gossypol, a disesquiterpene extracted from cotton seeds, is known to inhibit strongly the Plasmodium falciparum lactate dehydrogenase, but its high toxicity has stopped any antimalarial drug development. A series of Schiffs bases was synthesized from gossypol by modification of the aldehyde groups responsible for its toxicity. A total of 13 compounds showing low cytotoxicity were then selected and were compared with gossypol for activity against 2 chloroquine-resistant strains of P. falciparum (PFB, FCB1). These in vitro activities were evaluated using an isotope-based drug-susceptibility semiautomated microdilution test followed by determination of IC50 values (50% inhibitory concentration). In all, 12 of the 13 compounds tested were active; 3 of them displayed antimalarial activity comparable with that of gossypol itself.
Razakantoanina
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CNRS Laboratoire de Biologie parasitaire, Museum National d'Histoire Naturelle, Paris, France.
Nguyen Kim
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Jaureguiberry
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D000818:Animals; D000962:Antimalarials / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D006072:Gossypol / Q000031:analogs & derivatives*; D010963:Plasmodium falciparum / Q000187:drug effects*; D013329:Structure-Activity Relationship
D000962:Antimalarials; D006072:Gossypol