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Natural and semisynthetic analogues of manadoperoxide B reveal new structural requirements for trypanocidal activity
Giuseppina Chianese1, Fernando Scala, Barbara Calcinai
1Department of Pharmacy, University of Naples "Federico II", Via D. Montesano 49, Naples I-80131, Italy.
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.
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