Antimalarial Polyketide Cycloperoxides from the Marine Sponge Plakortis simplex

Three new (5-7) and two known (4 and 8) polyketide derivatives have been isolated from the Caribbean sponge Plakortis simplex. Their stereostructures have been determined by spectroscopic methods and chemical transformations, including Zn-mediated reduction, Dess-Martin oxidation, and application of Mosher’s method. The cycloperoxide derivatives plakortide Q (7) and compound 8 were evaluated for their in vitro antimalarial activity against chloroquine-sensitive and chloroquine-resistant strains of Plasmodium falciparum. The lower potency of these molecules compared to plakortin indicates that the change of configuration at C-3 exerts negative effects on the antimalarial activity