Synthesis and antiangiogenic activity of new silybin galloyl esters

J Med Chem. 2011 Oct 27;54(20):7397-407. doi: 10.1021/jm201034h. Epub 2011 Oct 3.


The synthesis of various silybin monogalloyl esters was developed, and their antiangiogenic activities were evaluated in a variety of in vitro tests with human umbilical vein endothelial cells (HUVECs). A structure-activity relationship (SAR) study found the regioselectivity of the silybin galloylation to be highly significant. Silybin (as an equimolar mixture of two diastereomers A and B) exhibited quite poor antiangiogenic activities, whereas its B stereoisomer is more active than silybin A. The galloylation of phenolic OH groups of natural silybin (a mixture of both isomers) leads to increases in their antiangiogenic activities, which is more apparent with the 7-OH than the 20-OH. In contrast, gallates at aliphatic OH groups either had a comparable activity to the parent compound or are even worse than silybin, which was observed in the case of 3-O-galloylsilybin. The most effective compound from this series (7-O-galloylsilybin) has also been prepared from stereochemically pure silybins A and B to evaluate the effect of stereochemistry on the activity. As with silybin itself, the B isomer of 7-O-galloylsilybin was more active than the A isomer.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Angiogenesis Inhibitors / chemical synthesis*
  • Angiogenesis Inhibitors / chemistry
  • Angiogenesis Inhibitors / pharmacology
  • Cell Differentiation / drug effects
  • Cell Movement / drug effects
  • Cell Proliferation / drug effects
  • Collagen
  • Drug Combinations
  • Endothelial Cells / drug effects
  • Endothelial Cells / physiology
  • Esters
  • Gallic Acid / analogs & derivatives*
  • Gallic Acid / chemical synthesis*
  • Gallic Acid / pharmacology
  • Human Umbilical Vein Endothelial Cells
  • Humans
  • Laminin
  • Proteoglycans
  • Silybin
  • Silymarin / analogs & derivatives*
  • Silymarin / chemical synthesis
  • Silymarin / pharmacology
  • Stereoisomerism
  • Structure-Activity Relationship


  • 7-O-galloylsilybin
  • Angiogenesis Inhibitors
  • Drug Combinations
  • Esters
  • Laminin
  • Proteoglycans
  • Silymarin
  • matrigel
  • Silybin
  • Gallic Acid
  • Collagen