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Structure-property relationships of trimetazidine derivatives and model compounds as potential antioxidants
|Published in||Free Radical Biology and Medicine. 1998, vol. 25, no. 1, p. 113-120|
|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.|
|Keywords||Antioxidants/*chemistry — Bepridil/analogs & derivatives/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/*chemistry — Vitamin E/chemistry|