Structure-property relationships of trimetazidine derivatives and model compounds as potential antioxidants

Free Radic Biol Med. 1998 Jul 1;25(1):113-20. doi: 10.1016/s0891-5849(98)00072-0.

Abstract

Twenty-five compounds (trimetazidine derivatives and other compounds, mostly having a free phenolic group) were examined for their radical scavenging and antioxidant properties. Their reaction with DPPH (2,2-diphenyl-1-picrylhydrazyl) as a measure of radical scavenging capacity was assessed by two parameters, namely EC50 (the concentration of antioxidant decreasing DPPH by 50%), and log Z, a kinetic parameter proposed here and derived from initial second-order rate constants and antioxidant/DPPH ratios. Antioxidant activities were determined by the inhibition of lipid peroxidation and albumin oxidation. The most active compounds were derivatives having a trolox or hydroquinone moiety. Physicochemical and structural properties were determined by molecular modeling as lipophilicity (virtual log P calculations) and H-Surf (solvent-accessible surface of hydroxyl hydrogen) and by quantum mechanical calculations (deltaH(ox) = oxidation enthalpy; deltaH(abs) = enthalpy of hydrogen abstraction). QSAR models were derived to identify molecular mechanisms responsible for the reactivity toward the DPPH radical and for the inhibition of lipid peroxidation. A useful prediction of antioxidant capacity could be achieved from calculated molecular properties and the kinetic parameter developed here.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antioxidants / chemistry*
  • Bepridil / analogs & derivatives
  • Bepridil / metabolism
  • Biphenyl Compounds
  • Computer Simulation
  • Cresols / chemistry
  • Free Radical Scavengers / chemistry
  • Free Radicals / metabolism
  • Hydroquinones / chemistry
  • Models, Chemical*
  • Phenols / chemistry
  • Picrates*
  • Structure-Activity Relationship
  • Trimetazidine / analogs & derivatives*
  • Trimetazidine / chemistry*
  • Vitamin E / chemistry

Substances

  • Antioxidants
  • Biphenyl Compounds
  • Cresols
  • Free Radical Scavengers
  • Free Radicals
  • Hydroquinones
  • Phenols
  • Picrates
  • Vitamin E
  • Bepridil
  • 1,1-diphenyl-2-picrylhydrazyl
  • Trimetazidine