Natural and Semisynthetic Analogues of Manadoperoxide B Reveal New Structural Requirements for Trypanocidal Activity

Abstract

Chemical analysis of the Indonesian sponge Plakortis cfr. lita afforded two new analogues of the potent trypanocidal agent manadoperoxide B (1), namely 12-isomanadoperoxide B (2) and manadoperoxidic acid B (3). These compounds were isolated along with a new short chain dicarboxylate monoester (4), bearing some interesting relationships with the polyketide endoperoxides found in this sponge. Some semi-synthetic analogues of manadoperoxide B (6–8) were prepared and evaluated for antitrypanosomal activity and cytotoxicity. These studies revealed crucial structure–activity relationships that should be taken into account in the design of optimized and simplified endoperoxyketal trypanocidal agents.

Keywords

• manadoperoxide B
• marine antitrypanosomals
• structure–activity relationships