海洋天然产物马勒万德 D 的全合成及细胞毒性研究和光致反应类似物。
Total synthesis and cytotoxicity of the marine natural product malevamide D and a photoreactive analog.
机构信息
Institute of Organic Chemistry, TU Braunschweig, Hagenring 30, 38106 Braunschweig, Germany.
Oncotest Institute for Experimental Oncology GmbH, Am Flughafen 12-14, 79108 Freiburg, Germany.
出版信息
Beilstein J Org Chem. 2014 Feb 3;10:316-22. doi: 10.3762/bjoc.10.29. eCollection 2014.
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.
首次对来自水云涡鞭藻的海洋天然产物马勒维亚酰胺 D 进行了全合成。最终的肽键偶联连接了 dolaisoleuine 和 dolaproine 亚基。马勒维亚酰胺 D 的苯环基团也被带有光反应性重氮甲烷部分的功能化，该部分经过了七个反应步骤。在一组 42 个人类癌细胞系中对细胞毒性进行全面评估，结果显示马勒维亚酰胺 D 的几何均数 IC70 值为 1.5 nM（IC50 为 0.7 nM），而光反应性衍生物的活性则至少降低了 200 倍。COMPARE 分析表明，马勒维亚酰胺 D 的作用模式可能是与微管蛋白相互作用。
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