Novel isomarabarican triterpenes, exhibiting selective anti-proliferative activity against vascular endothelial cells, from marine sponge Rhabdastrella globostellata.
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.
Aoki
Shunji
S
Graduate School of Pharmaceutical Sciences, Osaka University, Yamada-oka 1-6, Suita, Osaka 565-0871, Japan.
Sanagawa
Mami
M
Watanabe
Yasuo
Y
Setiawan
Andi
A
Arai
Masayoshi
M
Kobayashi
Motomasa
M
D000818:Animals; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D042783:Endothelial Cells / Q000166:cytology* / Q000187:drug effects*; D004952:Esters / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology; D006801:Humans; D007536:Isomerism; D009682:Magnetic Resonance Spectroscopy; D008745:Methylation; D008958:Models, Molecular; D015394:Molecular Structure; D009792:Oceans and Seas; D011161:Porifera / Q000737:chemistry*; D013329:Structure-Activity Relationship; D014315:Triterpenes / Q000737:chemistry* / Q000302:isolation & purification / Q000494:pharmacology*
D004952:Esters; D014315:Triterpenes