Total synthesis and cytotoxicity of the marine natural product malevamide D and a photoreactive analog

The marine natural product malevamide D from the cyanobacterium Symploca hydnoides was synthesized for the first time. The final peptide coupling linked the dolaisoleuine and dolaproine subunits. The phenyl group of malevamide D was also functionalized with a photoreactive diazirine moiety, which wa...

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Bibliographic Details
Published in:Beilstein journal of organic chemistry 2014-02, Vol.10 (1), p.316-322
Main Authors: Telle, Werner, Kelter, Gerhard, Fiebig, Heinz-Herbert, Jones, Peter G, Lindel, Thomas
Format: Article
Language:English
Subjects:
Chemistry
cytotoxicity
diazirines
dolastatin analogs
Full Research Paper
marine natural products
peptides
total synthesis
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Summary:The marine natural product malevamide D from the cyanobacterium Symploca hydnoides was synthesized for the first time. The final peptide coupling linked the dolaisoleuine and dolaproine subunits. The phenyl group of malevamide D was also functionalized with a photoreactive diazirine moiety, which was carried through seven reaction steps. Comprehensive assessment of the cytotoxicity in a panel of 42 human cancer cell lines revealed a geomean IC70 value of 1.5 nM (IC50 0.7 nM) for malevamide D, whereas the photoreactive derivative proved to be less active by a factor of at least 200. COMPARE analysis indicated tubulin interaction as likely mode of action of malevamide D.
ISSN:1860-5397
1860-5397
DOI:10.3762/bjoc.10.29