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

ABSTRACT: 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.

SUBMITTER: Telle W

PROVIDER: S-EPMC3943603 | biostudies-literature | 2014

REPOSITORIES: biostudies-literature

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

Telle Werner W Kelter Gerhard G Fiebig Heinz-Herbert HH Jones Peter G PG Lindel Thomas T

Beilstein journal of organic chemistry 20140203

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, wh ...[more]

PMID: 24605152

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