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 that include Zn-mediated reduction and Dess-Martin oxidation, and by 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 relative to plakortin indicates that the change of configuration at C-3 exerts negative effects on the antimalarial activity.