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

Novel isomarabarican triterpenes, exhibiting selective anti-proliferative activity against vascular endothelial cells, from marine sponge Rhabdastrella globostellata
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DOI:
10.1016/j.bmc.2007.04.070
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发表时间:
2007-07-15
影响因子:
3.5
通讯作者:
Kobayashi, Motomasa
Kobayashi, Motomasa
中科院分区:
医学3区
文献类型:
--
作者:
Aoki, Shunji;Sanagawa, Mami;Kobayashi, Motomasa

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从海绵Rhabdastrella globostellata中分离出四个具有异阿拉伯聚糖型三萜骨架的新型globostellatic acid X甲酯(1-4)和三个相关新化合物(5-7),作为针对人脐静脉内皮细胞(HUVEC)的选择性抗增殖剂。通过详细的2D NMR分析来阐明这些化学结构。发现具有13 E-几何构型的两种globostellate酸X甲基酯(3和4)与几种其他细胞系相比选择性地抑制HUVEC的增殖80至250倍。13 E,17 E-Globostellate acid X methyl ester(4)也抑制bFGF诱导的肾小管形成和VEGF诱导的HUVEC迁移。此外,4诱导HUVECs凋亡,而它对VEGF诱导的HUVECs中ERK 1/2磷酸化没有影响。(c)2007爱思唯尔有限公司保留所有权利。
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. (c) 2007 Elsevier Ltd. All rights reserved.