Artemisinin and a series of novel endoperoxide antimalarials exert early effects on digestive vacuole morphology.

ABSTRACT: Artermisinin and its derivatives are now the mainstays of antimalarial treatment; however, their mechanism of action is only poorly understood. We report on the synthesis of a novel series of epoxy-endoperoxides that can be prepared in high yields from simple starting materials. Endoperoxides that are disubstituted with alkyl or benzyl side chains show efficient inhibition of the growth of both chloroquine-sensitive and -resistant strains of Plasmodium falciparum. A trans-epoxide with respect to the peroxide linkage increases the activity compared to that of its cis-epoxy counterpart or the parent endoperoxide. The novel endoperoxides do not show a strong interaction with artemisinin. We have compared the mechanism of action of the novel endoperoxides with that of artemisinin. Electron mic

SUBMITTER: del Pilar Crespo M 

PROVIDER: S-EPMC2223901 | biostudies-literature | 2008 Jan

REPOSITORIES: biostudies-literature