Cortistatins A, B, C, and D, anti-angiogenic steroidal alkaloids, from the marine sponge Corticium simplex
Cortistatins A, B, C, and D, anti-angiogenic steroidal alkaloids, from the marine sponge Corticium simplex
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DOI：
10.1021/ja057404h
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发表时间：
2006-03-15
影响因子：
15
通讯作者：
Kobayashi, M
中科院分区：
文献类型：
--
作者：
Aoki, S;Watanabe, Y;Kobayashi, M
从海绵corticiumsimplex中分离到四种新的甾体生物碱，分别命名为A(1)、B(2)、C(3)和D(4)，它们由9(10−19)-正雄甾烷和异喹啉骨架组成。通过详细的二维核磁共振、CD和x射线晶体学分析，阐明了1−4的绝对立体结构。皮质抑素A−D对人脐静脉内皮细胞（HUVECs）的增殖具有高选择性抑制作用。四种物质中，皮质抑素A(1)对HUVECs的抗增殖活性最强（IC50= 0.0018 μM），与正常成纤维细胞或几种肿瘤细胞系相比，其选择性指数在3000倍以上。
Four novel steroidal alkaloids named cortistatins A (1), B (2), C (3), and D (4) consisting of a 9(10−19)-abeo-androstane and isoquinoline skeleton have been isolated from the marine spongeCorticiumsimplex. The absolute stereostructures of1−4were elucidated by detailed 2D NMR, CD, and X-ray crystallographic analyses. Cortistatins A−D inhibited proliferation of human umbilical vein endothelial cells (HUVECs) with high selectivity. Among the four substances, cortistatin A (1) showed the strongest anti-proliferative activity (IC50= 0.0018 μM) against HUVECs, in which the selective index was more than 3000-fold in comparison with that of normal fibroblast or several tumor cell lines.