Structure–activity relationship and biological property of cortistatins, anti-angiogenic spongean steroidal alkaloids
- 作者：Shunji Aoki ; Yasuo Watanabe ; Daiki Tanabe ; Masayoshi Arai ; Hideaki Suna ; Katsushiro Miyamoto ; Hiroshi Tsujibo ; Kazutake Tsujikawa ; Hiroshi Yamamoto ; Motomasa Kobayashi
- 关键词：Cortistatin ; Marine sponge ; Anti-angiogenic effect ; HUVECs ; Tubular formation ; Migration
- 刊名：Bioorganic and Medicinal Chemistry
- 出版年：2007
- 期刊代码：9_09680896
- 类别：ch
- 出版时间：1 November 2007
- 卷：15
- 期：21
- 页码：6758-6762
- 文件大小：453 K
摘要
Previously, bioassay-guided separation led us to isolate eleven novel steroidal alkaloids named cortistatins from the marine sponge Corticium simplex. These cortistatins were classified into three types based on the chemical structure of the side chain part, that is, isoquinoline, N-methyl piperidine or 3-methylpyridine units. From the structure–activity relationship study, the isoquinoline unit in the side chain was found to be crucial for the anti-angiogenic activity of cortistatins. Cortistatin A (1) showed cytostatic growth-inhibitory activity against human umbilical vein endothelial cells (HUVECs). Cortistatin A (1) also inhibited VEGF-induced migration of HUVECs and bFGF-induced tubular formation. Although cortistatin A (1) showed no effect on VEGF-induced phosphorylation of ERK1/2 and p38, which are one of the signaling pathways for migration and tubular formation, the phosphorylation of the unidentified 110 kDa protein in HUVECs was inhibited by the treatment with cortistatin A.