Discovery, characterization, and structure - Activity relationships studies of proapoptotic polyphenols targeting B-cell lymphocyte/leukemia-2 proteins
Discovery, characterization, and structure - Activity relationships studies of proapoptotic polyphenols targeting B-cell lymphocyte/leukemia-2 proteins
复制标题
DOI：
10.1021/jm030190z
复制
发表时间：
2003-09-25
影响因子：
7.3
通讯作者：
Pellecchia, M
中科院分区：
文献类型：
--
作者：
Kitada, S;Leone, M;Pellecchia, M
在最有前途的化学预防药物中，某些天然多酚类物质因其抑制肿瘤发生的活性而受到广泛关注。鉴于它们的抗癌特性，这些化合物作为潜在的化疗药物也有很大的前景。然而，要将这些化学预防剂转化为化学治疗化合物，必须描述它们的确切作用机制。通过使用现代核磁共振波谱技术、荧光偏振位移测定和基于细胞的测定指导下的多学科方法，我们已经开始揭示某些多酚的作用机制，如棉酚（一种从棉籽提取物中提取的化合物）和Purpurogallin（一种从胡桃木中提取的天然化合物）及其衍生物。我们的研究结果表明，这些天然产物结合并拮抗b细胞淋巴细胞/白血病-2 （Bcl-2）家族蛋白如Bcl-x(L)的抗凋亡作用。我们的体外和体内数据不仅为用这些化合物开发新的癌症治疗方法打开了机会之窗，而且还提供了结构信息，可用于设计和开发新的和更有效的类似物。
Among the most promising chemopreventive agents, certain natural polyphenols have recently received a great deal of attention because of their demonstrated inhibitory activity against tumorigenesis. In view of their anticancer properties, these compounds also hold great promise as potential chemotherapeutic agents. However, to translate these chemopreventive agents into chemotherapeutic compounds, their exact mechanisms of action must be delineated. By using a multidisciplinary approach guided by modern nuclear magnetic resonance spectroscopy techniques, fluorescence polarization displacement assays, and cell-based assays, we have begun to unravel the mechanisms of actions of certain polyphenols such as Gossypol (a compound from cotton seed extracts) and Purpurogallin (a natural compound extracted from Quercus sp. nutgall) and their derivatives. Our findings suggest that these natural products bind and antagonize the antiapoptotic effects of B-cell lymphocyte/leukemia-2 (Bcl-2) family proteins such as Bcl-x(L). Our in vitro and in vivo data not only open a window of opportunities for the development of novel cancer treatments with these compounds but also provide structural information that can be used for the design and development of novel and more effective analogues.