Antimalarial sulfide, sulfone, and sulfonamide trioxanes Original Research Article

A series of trioxanes featuring sulfide, sulfone, and sulfonamide substituents in diverse positions has been prepared. Structure–activity relationship (SAR) generalizations highlight two major factors controlling the antimalarial potency of these new chemical entities: (1) the proximity of the sulfur-containing substituent to the crucial peroxide bond and (2) the oxidation state of the sulfur-containing substituent. Generally, sulfones are more antimalarially potent than the corresponding sulfides.