Novel 3,5-diaryl pyrazolines and pyrazole as low-density lipoprotein (LDL) oxidation inhibitor

Bioorg Med Chem Lett. 2004 Jun 7;14(11):2719-23. doi: 10.1016/j.bmcl.2004.03.072.

Abstract

Compounds 4a-j and 5 were synthesized by cyclocondensation of 3a-j and hydrazine and showed significant LDL-antioxidant activities in the TBARS assay, the lag time of conjugated diene production, the relative electrophoretic mobility (REM) of ox-LDL, the apoB-100 fragmentation, and the macrophage-mediated LDL oxidation. Among compounds 4a-j and 5, 4a was found to be the most active compound as an inhibitor of LDL oxidation and 4a (IC50 = 0.1 microM) was 6-fold more potent than probucol (IC50 = 0.6 microM) in the TBARS assay.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antioxidants / chemical synthesis*
  • Antioxidants / pharmacology
  • Copper / pharmacology
  • Humans
  • Inhibitory Concentration 50
  • Lipid Peroxidation / drug effects
  • Lipoproteins, LDL / antagonists & inhibitors
  • Lipoproteins, LDL / drug effects*
  • Lipoproteins, LDL / metabolism
  • Macrophages / metabolism
  • Oxidation-Reduction
  • Pyrazoles / chemical synthesis
  • Pyrazoles / pharmacology*
  • Thiobarbituric Acid Reactive Substances

Substances

  • Antioxidants
  • Lipoproteins, LDL
  • Pyrazoles
  • Thiobarbituric Acid Reactive Substances
  • oxidized low density lipoprotein
  • Copper