Structure-related cytotoxic activity of derivatives from kulokekahilide-2, a cyclodepsipeptide in Hawaiian marine mollusk.
Structure-related cytotoxic activity of derivatives from kulokekahilide-2, a cyclodepsipeptide in Hawaiian marine mollusk.
复制标题
kulokekahilide-2（夏威夷海洋软体动物中的一种环缩肽）衍生物的结构相关细胞毒活性。
DOI：
10.1016/j.bmcl.2012.10.058
复制
发表时间：
2012
影响因子：
2.7
通讯作者：
Umehara M
中科院分区：
文献类型：
--
作者：
Tue;N.M.;Suzuki;G.;Takahashi;S.;Kannan;K.;Takigami;H.;Tanabe;S.;金允喜;Umehara M
Kulokekahilide-2是从夏威夷海洋软体动物中分离得到的一种26元环缩肽，对哺乳动物肿瘤细胞具有较强的细胞毒性。在本研究中，我们合成了kulokekahilide-2及其衍生物，并研究了这些肽在人癌细胞（A549，K562和MCF 7细胞）中的构效关系。本研究表明，缩肽的环化和21位Ala的手性对kulokekahilide-2的细胞毒活性有重要影响，在24-d-MePhe苯基帕拉引入卤素可显著提高kulokekahilide-2及其衍生物的细胞毒活性。这些结果表明，对kulokekahilide-2中的24-d-MePhe进行修饰，保留其环化和21位的手性，是开发kulokekahilide-2新衍生物作为抗肿瘤药物的有希望的策略。
Kulokekahilide-2, a 26-membered cyclodepsipeptide, was isolated from Hawaiian marine mollusk and possessed potent cytotoxicity in mammalian tumor cells. In the present study, we synthesized kulokekahilide-2 and its derivatives and examined the structure–activity relationships of these peptides in human cancer cells (A549, K562, and MCF7 cells). This study demonstrated that the cyclization of depsipeptide and the chirality of the 21 position in Ala in kulokekahilide-2 were important for its cytotoxic property and that addition of halogen at the para position of phenyl group in the 24-d-MePhe in kulokekahilide-2 as well as some derivatives remarkably increased their cytotoxicity in human cancer cells. These results suggest that the modifications of 24-d-MePhe in kulokekahilide-2, preserving its cyclization and the chirality at the 21-position, are promising strategy for exploring new derivative of kulokekahilide-2 as anti-tumor drug.