Ligustrazine derivatives. Part 4: design, synthesis, and biological evaluation of novel ligustrazine-based stilbene derivatives as potential cardiovascular agents

Chem Biol Drug Des. 2012 May;79(5):731-9. doi: 10.1111/j.1747-0285.2012.01332.x. Epub 2012 Feb 15.

Abstract

A series of novel stilbene derivatives containing ligustrazinyl moiety was designed, synthesized, and assayed for their protective effects on damaged endothelial cells. The results showed that most ligustrazinyl stilbene derivatives exhibited high protective effects on the human umbilical vascular endothelial cells (HUVECs) damaged by hydrogen peroxide in comparison with Ligustrazine. The stilbene derivatives A6, A9, A11, A21, A24, A25, and A27 exhibited high potency with low EC(50) values ranged from 0.0249 μm to 0.0898 mm. Compound A27 displayed EC(50) 0.0249 μm, which is 30,000 times higher than that of Ligustrazine, presenting a most promising lead for further investigation. Structure-activity relationships were briefly discussed.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cardiovascular Agents / chemical synthesis
  • Cardiovascular Agents / chemistry*
  • Cardiovascular Agents / pharmacology*
  • Drug Design
  • Human Umbilical Vein Endothelial Cells / drug effects
  • Human Umbilical Vein Endothelial Cells / pathology
  • Humans
  • Hydrogen Peroxide / metabolism
  • Oxidative Stress / drug effects
  • Pyrazines / chemical synthesis
  • Pyrazines / chemistry*
  • Pyrazines / pharmacology*
  • Stilbenes / chemical synthesis
  • Stilbenes / chemistry*
  • Stilbenes / pharmacology*
  • Structure-Activity Relationship

Substances

  • Cardiovascular Agents
  • Pyrazines
  • Stilbenes
  • Hydrogen Peroxide
  • tetramethylpyrazine