Design, synthesis, and biological activities of novel Ligustrazine derivatives

Bioorg Med Chem. 2007 May 15;15(10):3315-20. doi: 10.1016/j.bmc.2007.03.033. Epub 2007 Mar 15.

Abstract

A series of novel Ligustrazine derivatives was designed, synthesized, and assayed for their protective effects on damaged ECV-304 cells and antiplatelet aggregation activities. The results showed that most Ligustrazine derivatives exhibited lower EC(50) values for protective effects on the ECV-304 cells damaged by hydrogen peroxide in comparison with Ligustrazine. And some Ligustrazine derivatives presented better antiplatelet aggregation activities than Ligustrazine. The derivatives containing the bisphenylmethyl pharmacophore (7a-c) exhibited highest potency. Compound 7a displayed most potential protective effects on the ECV-304 cells damaged by hydrogen peroxide, and compound 7c was found to be the most active antiplatelet aggregation agent. Structure-activity relationships were briefly discussed.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Blood Platelets / drug effects
  • Cell Line
  • Chromatography, Thin Layer
  • Drug Design
  • Endothelial Cells / drug effects*
  • Humans
  • Hydrogen Peroxide / antagonists & inhibitors
  • Hydrogen Peroxide / toxicity
  • In Vitro Techniques
  • Indicators and Reagents
  • Magnetic Resonance Spectroscopy
  • Mass Spectrometry
  • Oxidants / antagonists & inhibitors
  • Oxidants / toxicity
  • Platelet Aggregation Inhibitors / chemical synthesis*
  • Platelet Aggregation Inhibitors / pharmacology*
  • Pyrazines / chemical synthesis*
  • Pyrazines / pharmacology*
  • Rabbits
  • Spectrometry, Mass, Electrospray Ionization
  • Spectrophotometry, Infrared
  • Spectroscopy, Fourier Transform Infrared

Substances

  • Indicators and Reagents
  • Oxidants
  • Platelet Aggregation Inhibitors
  • Pyrazines
  • Hydrogen Peroxide
  • tetramethylpyrazine