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

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

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Proliferation / drug effects
  • Cells, Cultured
  • Endothelial Cells / cytology*
  • Endothelial Cells / drug effects*
  • Esters / chemistry
  • Esters / isolation & purification
  • Esters / pharmacology
  • Humans
  • Isomerism
  • Magnetic Resonance Spectroscopy
  • Methylation
  • Models, Molecular
  • Molecular Structure
  • Oceans and Seas
  • Porifera / chemistry*
  • Structure-Activity Relationship
  • Triterpenes / chemistry*
  • Triterpenes / isolation & purification
  • Triterpenes / pharmacology*

Substances

  • Esters
  • Triterpenes