Issue 35, 2012

Manadoperoxides, a new class of potent antitrypanosomal agents of marine origin

Abstract

Chemical investigation of the marine sponge Plakortis cfr. lita afforded a library of endoperoxyketal polyketides, manadoperoxides B–K (3–5 and 7–13) and peroxyplakoric esters B3 (6) and C (14). Eight of these metabolites are new compounds and some contain an unprecedented chlorine-bearing THF-type ring in the side chain. The library of endoperoxide derivatives was evaluated for in vitro activity against Trypanosoma brucei rhodesiense and Leishmania donovani. Some compounds, such as manadoperoxide B, exhibited ultrapotent trypanocidal activity (IC50 = 3 ng mL−1) without cytotoxicity. Detailed examination of the antitrypanosomal activity data and comparison with those available in the literature for related dioxane derivatives enabled us to draw a series of structure–activity relationships. Interestingly, it appears that minor structural changes, such as a shift of the methyl group around the dioxane ring, can dramatically affect the antitrypanosomal activity. This information can be valuable to guide the design of optimized antitrypanosomal agents based on the dioxane scaffold.

Graphical abstract: Manadoperoxides, a new class of potent antitrypanosomal agents of marine origin

Supplementary files

Article information

Article type
Paper
Submitted
12 Jun 2012
Accepted
06 Jul 2012
First published
12 Jul 2012

Org. Biomol. Chem., 2012,10, 7197-7207

Manadoperoxides, a new class of potent antitrypanosomal agents of marine origin

G. Chianese, E. Fattorusso, F. Scala, R. Teta, B. Calcinai, G. Bavestrello, H. A. Dien, M. Kaiser, D. Tasdemir and O. Taglialatela-Scafati, Org. Biomol. Chem., 2012, 10, 7197 DOI: 10.1039/C2OB26124C

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