Antioxydant activity of β-carboline derivatives in the LDL oxidation model

Eur J Med Chem. 2011 Jun;46(6):2575-85. doi: 10.1016/j.ejmech.2011.03.048. Epub 2011 Mar 30.

Abstract

A series of β-carboline compounds were synthesized, starting from compound GWC22, their antioxidant activity was determined by inhibition of lipid peroxidation. The oxidation of LDL was induced in the presence of CuSO4 or 2,2'-azobis(2-amidinopropane) dihydrochloride (AAPH). The protective actions of these compounds against the cytotoxicity were evaluated with lactate dehydrogenase (LDH) activity in bovine aortic endothelial cells (BAECs) and cellular vitality by measuring mitochondrial activity in the presence of MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide). Most of compounds showed an higher antioxidant activity than GWC22 derivative (R=1.6 for 5 μM CuSO4). The best antioxidant activities are phenolic and benzyloxy derivatives with ratio R=1.9 to 2.8 for 1 μM CuSO4. These substances have protective actions and increase significantly the cell viability.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antioxidants / chemical synthesis
  • Antioxidants / chemistry
  • Antioxidants / pharmacology*
  • Aorta / cytology
  • Aorta / drug effects
  • Aorta / enzymology
  • Carbolines / chemical synthesis
  • Carbolines / chemistry
  • Carbolines / pharmacology*
  • Cattle
  • Cell Survival / drug effects
  • Cholesterol, LDL / chemistry
  • Cholesterol, LDL / drug effects
  • Cholesterol, LDL / metabolism*
  • Dose-Response Relationship, Drug
  • Drug Evaluation, Preclinical
  • Endothelial Cells / drug effects
  • Endothelial Cells / metabolism
  • L-Lactate Dehydrogenase / metabolism
  • Lipid Peroxidation / drug effects*
  • Mitochondria / drug effects
  • Mitochondria / metabolism
  • Models, Biological*
  • Molecular Structure
  • Oxidation-Reduction
  • Stereoisomerism
  • Structure-Activity Relationship

Substances

  • Antioxidants
  • Carbolines
  • Cholesterol, LDL
  • L-Lactate Dehydrogenase