title: 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.affiliation: Institute of Organic Chemistry, TU Braunschweig, Hagenring 30, 38106 Braunschweig, Germany.
authors.forename: Werner
authors.initials: W
authors.lastname: Telle
authors.affiliation: Oncotest Institute for Experimental Oncology GmbH, Am Flughafen 12-14, 79108 Freiburg, Germany.
authors.forename: Gerhard
authors.initials: G
authors.lastname: Kelter
authors.affiliation: Oncotest Institute for Experimental Oncology GmbH, Am Flughafen 12-14, 79108 Freiburg, Germany.
authors.forename: Heinz-Herbert
authors.initials: HH
authors.lastname: Fiebig
authors.affiliation: Institute of Inorganic and Analytical Chemistry, TU Braunschweig, Hagenring 30, 38106 Braunschweig, Germany.
authors.forename: Peter G
authors.initials: PG
authors.lastname: Jones
authors.affiliation: Institute of Organic Chemistry, TU Braunschweig, Hagenring 30, 38106 Braunschweig, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Lindel
keywords: cytotoxicity; diazirines; dolastatin analogs; marine natural products; peptides; total synthesis