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

2007; Elsevier BV; Volume: 15; Issue: 14 Linguagem: Inglês

10.1016/j.bmc.2007.04.070

1464-3391

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

Invertebrate Immune Response Mechanisms

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.