Structure-activity relationship and biological property of cortistatins, anti-angiogenic spongean steroidal alkaloids
Structure-activity relationship and biological property of cortistatins, anti-angiogenic spongean steroidal alkaloids
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DOI：
10.1016/j.bmc.2007.08.017
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发表时间：
2007-11-01
影响因子：
3.5
通讯作者：
Kobayashi, Motomasa
中科院分区：
文献类型：
--
作者：
Aoki, Shunji;Watanabe, Yasuo;Kobayashi, Motomasa
在此之前，生物测定引导的分离使我们从海绵Corticium simplex中分离出11种新的甾体生物碱，命名为cortisetatin。根据侧链部分的化学结构将这些皮质抑素分为三种类型。即异喹啉、N-甲基哌啶或3-甲基吡啶单元。从构效关系的研究，异喹啉单元的侧链被发现是至关重要的抗血管生成活性的皮质抑素。Cortistatin A（1）对人脐静脉内皮细胞（HUVECs）具有细胞生长抑制活性。Cortistatin A（1）也抑制VEGF诱导的HUVECs迁移和bFGF诱导的肾小管形成。虽然皮质抑素A（1）对VEGF诱导的ERK 1/2和p38磷酸化没有影响，但这两种蛋白是迁移和肾小管形成的信号通路之一，但皮质抑素A处理抑制了HUVECs中未鉴定的110 kDa蛋白的磷酸化。(C)2007爱思唯尔有限公司版权所有。
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. (C) 2007 Elsevier Ltd. All rights reserved.