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

被引：4

作者：

Telle, Werner ^{[1
]}

Kelter, Gerhard ^{[2
]}

Fiebig, Heinz-Herbert ^{[2
]}

Jones, Peter G. ^{[3
]}

Lindel, Thomas ^{[1
]}

机构：

[1] Tech Univ Carolo Wilhelmina Braunschweig, Inst Organ Chem, D-38106 Braunschweig, Germany

[2] Oncotest Inst Expt Oncol GmbH, D-79108 Freiburg, Germany

[3] Tech Univ Carolo Wilhelmina Braunschweig, Inst Inorgan & Analyt Chem, D-38106 Braunschweig, Germany

来源：

BEILSTEIN JOURNAL OF ORGANIC CHEMISTRY | 2014年 / 10卷

关键词：

cytotoxicity; diazirines; dolastatin analogs; marine natural products; peptides; total synthesis; CYANOBACTERIUM SYMPLOCA-HYDNOIDES; ISODOLASTATIN-H; DOLASTATIN; 10; AMINO-ACIDS; CONJUGATE; PEPTIDE; TUBULIN;

D O I：

10.3762/bjoc.10.29

中图分类号：

O62 [有机化学];

学科分类号：

070303 ; 081704 ;

摘要：

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.

引用

页码：316 / 322

页数：7

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