从海洋海绵球状横纹海绵中分离得到的新型异马巴拉坎三萜类化合物，对血管内皮细胞具有选择性抗增殖活性。

Novel isomarabarican triterpenes, exhibiting selective anti-proliferative activity against vascular endothelial cells, from marine sponge Rhabdastrella globostellata.

作者信息

Aoki Shunji, Sanagawa Mami, Watanabe Yasuo, Setiawan Andi, Arai Masayoshi, Kobayashi Motomasa

机构信息

Graduate School of Pharmaceutical Sciences, Osaka University, Yamada-oka 1-6, Suita, Osaka 565-0871, Japan.

出版信息

Bioorg Med Chem. 2007 Jul 15;15(14):4818-28. doi: 10.1016/j.bmc.2007.04.070. Epub 2007 May 6.

DOI:10.1016/j.bmc.2007.04.070

PMID:17524651

Abstract

Four novel globostellatic acid X methyl esters (1-4) having isomarabarican-type triterpenoidal skeleton and three related new compounds (5-7) were isolated from the marine sponge Rhabdastrella globostellata, as selective anti-proliferative agents against human umbilical vein endothelial cells (HUVECs). Those chemical structures were elucidated by the detailed 2D NMR analysis. Two globostellatic acid X methyl esters (3 and 4) having 13E-geometry were found to inhibit proliferation of HUVECs, 80- to 250-fold selectively in comparison with several other cell lines. 13E,17E-Globostellatic acid X methyl ester (4) also inhibited bFGF-induced tubular formation and VEGF-induced migration of HUVECs. Moreover, 4 induced apoptosis of HUVECs, whereas it exhibited no effect on VEGF-induced phosphorylation of ERK1/2 in HUVECs.

摘要

从海洋海绵球状星骨海绵（Rhabdastrella globostellata）中分离出四种具有异香树脂烷型三萜骨架的新型球状星骨酸X甲酯（1-4）以及三种相关的新化合物（5-7），它们是针对人脐静脉内皮细胞（HUVECs）的选择性抗增殖剂。通过详细的二维核磁共振分析阐明了这些化学结构。发现两种具有13E-构型的球状星骨酸X甲酯（3和4）与其他几种细胞系相比，能选择性地抑制HUVECs的增殖80至250倍。13E,17E-球状星骨酸X甲酯（4）还能抑制碱性成纤维细胞生长因子（bFGF）诱导的HUVECs管状形成以及血管内皮生长因子（VEGF）诱导的HUVECs迁移。此外，4能诱导HUVECs凋亡，而对VEGF诱导的HUVECs中细胞外信号调节激酶1/2（ERK1/2）的磷酸化没有影响。