ABSTRACT
Synthesis of a new family of quinolylhydrazone derivatives and evaluation of their activity against a chloroquine-resistant strain of Plasmodium falciparum are described. The best compound displayed an activity 6-fold higher than chloroquine. None of the active compounds were found to inhibit beta-hematin formation in vitro in the same range as chloroquine and five among them displayed lower calculated vacuolar accumulation ratios, suggesting the implication of a different mechanism of action.
Subject(s)
Antimalarials/chemical synthesis , Glyoxylates/chemical synthesis , Hydrazones/chemical synthesis , Animals , Antimalarials/pharmacology , Glyoxylates/pharmacology , Hydrazones/pharmacology , Plasmodium falciparum/drug effects , Plasmodium falciparum/growth & developmentABSTRACT
Solution-phase synthesis and evaluation of a library of 31 sulfonamides as inhibitors of a chloroquine-resistant strain of Plasmodium falciparum are described. The most potent compound displayed an activity 100-fold better than chloroquine. Experiments using a fluorescent sulfonamide derivative suggest that their site of action inside the parasite is different to that of chloroquine.
