Protective effects of 4-hydroxycinnamic ethyl ester derivatives and related dehydrodimers against oxidation of LDL: radical scavengers or metal chelators?
4-Hydroxycinnamate derivatives are known to be potent protectors against oxidation of low-density lipoproteins (LDL), via a combination of free radical scavenging and transition metal chelation. Through a series of 4-hydroxycinnamic ethyl ester derivatives and related 8-8 dehydrodimers, we have tried to bring out the structural requirements for radical scavenging and cupric ion chelation. We found that the monomeric compounds, except for highly lipophilic tert-butyl derivative 3, exhibited rather low radical scavenging properties. Furthermore, they did not chelate copper but, in contrast, reduced cupric ion to cuprous ion, affording the related 8-8 dehydrodimers, for which they could be considered as precursors in vitro. In the copper-dependent human LDL oxidation in vitro, the cyclic 8-8 dehydrodimer forms behaved essentially as efficient copper chelators, while related noncyclic 8-8 forms, which were found to be the best protectors, mainly acted as radical scavengers.
Neudörffer
Anne
A
Unité Mixte de Recherche CNRS-Université Paris 5 (UMR 8638, Synthèse et Structure de Molécules d'Intérêt Pharmacologique), Faculté des Sciences Pharmaceutiques et Biologiques, 4 Avenue de l'Observatoire, 75270 Paris Cedex 06, France.
Desvergne
Jean-Pierre
JP
Bonnefont-Rousselot
Dominique
D
Legrand
Alain
A
Fleury
Maurice-Bernard
MB
Largeron
Martine
M
D002614:Chelating Agents / Q000494:pharmacology*; D003300:Copper / Q000737:chemistry; D003373:Coumaric Acids / Q000737:chemistry / Q000494:pharmacology*; D019281:Dimerization; D004952:Esters / Q000494:pharmacology*; D016166:Free Radical Scavengers / Q000494:pharmacology*; D006801:Humans; D015227:Lipid Peroxidation / Q000187:drug effects*; D008077:Lipoproteins, LDL / Q000737:chemistry*; D011422:Propionates
D002614:Chelating Agents; D003373:Coumaric Acids; D004952:Esters; D016166:Free Radical Scavengers; D008077:Lipoproteins, LDL; D011422:Propionates; D003300:Copper; C495469:p-coumaric acid