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.

• Authors: Werner Telle, Gerhard Kelter, Heinz-Herbert Fiebig, Peter G Jones, Thomas Lindel
• Journal: Beilstein journal of organic chemistry (Beilstein J Org Chem) Vol. 10 Pg. 316-22 ( 2014) ISSN: 1860-5397 [Print] Germany
• PMID: 24605152 (Publication Type: Journal Article)