Display Settings:

Format

Send to:

Choose Destination
See comment in PubMed Commons below
Org Biomol Chem. 2012 Sep 21;10(35):7197-207. doi: 10.1039/c2ob26124c. Epub 2012 Aug 2.

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

Author information

  • 1Dipartimento di Chimica delle Sostanze Naturali, Universit√† di Napoli Federico II, Napoli, Italy.

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 B(3) (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 (IC(50) = 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.

PMID:
22859016
[PubMed - indexed for MEDLINE]
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for Royal Society of Chemistry
    Loading ...
    Write to the Help Desk