title: Structure-property relationships of trimetazidine derivatives and model compounds as potential antioxidants.
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.
authors.affiliation: Institut de Chimie Thérapeutique, Section de Pharmacie, Université de Lausanne, Switzerland.
authors.forename: J
authors.initials: J
authors.lastname: Ancerewicz
authors.forename: E
authors.initials: E
authors.lastname: Migliavacca
authors.forename: P A
authors.initials: PA
authors.lastname: Carrupt
authors.forename: B
authors.initials: B
authors.lastname: Testa
authors.forename: F
authors.initials: F
authors.lastname: Brée
authors.forename: R
authors.initials: R
authors.lastname: Zini
authors.forename: J P
authors.initials: JP
authors.lastname: Tillement
authors.forename: S
authors.initials: S
authors.lastname: Labidalle
authors.forename: D
authors.initials: D
authors.lastname: Guyot
authors.forename: A M
authors.initials: AM
authors.lastname: Chauvet-Monges
authors.forename: A
authors.initials: A
authors.lastname: Crevat
authors.forename: A
authors.initials: A
authors.lastname: Le Ridant
mesh_terms: D000975:Antioxidants / Q000737:chemistry*; D015764:Bepridil / Q000031:analogs & derivatives / Q000378:metabolism; D001713:Biphenyl Compounds; D003198:Computer Simulation; D003408:Cresols / Q000737:chemistry; D016166:Free Radical Scavengers / Q000737:chemistry; D005609:Free Radicals / Q000378:metabolism; D006873:Hydroquinones / Q000737:chemistry; D008956:Models, Chemical; D010636:Phenols / Q000737:chemistry; D010851:Picrates; D013329:Structure-Activity Relationship; D014292:Trimetazidine / Q000031:analogs & derivatives* / Q000737:chemistry*; D014810:Vitamin E / Q000737:chemistry
chemical_list: D000975:Antioxidants; D001713:Biphenyl Compounds; D003408:Cresols; D016166:Free Radical Scavengers; D005609:Free Radicals; D006873:Hydroquinones; D010636:Phenols; D010851:Picrates; D014810:Vitamin E; D015764:Bepridil; C004931:1,1-diphenyl-2-picrylhydrazyl; D014292:Trimetazidine