title: Synthesis, antioxidant and cytoprotective evaluation of potential antiatherogenic phenolic hydrazones. A structure-activity relationship insight.
abstract: A novel series of hydrazones derived from substituted benzaldehydes have been synthesized as potential antiatherogenic agents. Several methods were used for exploring their antioxidant and cytoprotective properties, such as their scavenging effect on 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical, the inhibition of superoxide anion (O₂(·-)) generation and the measurement of cell-induced low-density lipoprotein oxidation (monitored by the formation of TBARS). The cytoprotective efficacy was also evaluated by measuring the cell viability (monitored by the MTT assay) in the presence of cytotoxic oxidized LDL. In this report, we discuss the relationship between the chemical structure of phenolic hydrazones and their antioxidant and cytoprotective activities, for subsequent application as antiatherogenic agents. This SAR study confirms that the phenolic frame is not the only prerequisite for antioxidant activity and N-methylbenzothiazole hydrazone moiety magnifies the dual required properties in two most interesting derivatives.
authors.affiliation: Université Paul Sabatier Toulouse III, UMR 5068, Laboratoire de Synthèse et Physico-Chimie de Molécules d'Intérêt Biologique, 118, Route de Narbonne, F-31062 Toulouse Cedex 9, France; CNRS, UMR 5068, Laboratoire de Synthèse et Physico-Chimie de Molécules d'Intérêt Biologique, 118, Route de Narbonne, F-31062 Toulouse Cedex 9, France.
authors.forename: Corinne
authors.initials: C
authors.lastname: Vanucci-Bacqué
authors.affiliation: Université Paul Sabatier Toulouse III, UMR 5068, Laboratoire de Synthèse et Physico-Chimie de Molécules d'Intérêt Biologique, 118, Route de Narbonne, F-31062 Toulouse Cedex 9, France; CNRS, UMR 5068, Laboratoire de Synthèse et Physico-Chimie de Molécules d'Intérêt Biologique, 118, Route de Narbonne, F-31062 Toulouse Cedex 9, France.
authors.forename: Chantal
authors.initials: C
authors.lastname: Carayon
authors.affiliation: INSERM, UMR 1048, I2MC, BP 84225, 31432 Toulouse Cedex 4, France.
authors.forename: Corinne
authors.initials: C
authors.lastname: Bernis
authors.affiliation: INSERM, UMR 1048, I2MC, BP 84225, 31432 Toulouse Cedex 4, France.
authors.forename: Caroline
authors.initials: C
authors.lastname: Camare
authors.affiliation: INSERM, UMR 1048, I2MC, BP 84225, 31432 Toulouse Cedex 4, France.
authors.forename: Anne
authors.initials: A
authors.lastname: Nègre-Salvayre
authors.affiliation: Université Paul Sabatier Toulouse III, UMR 5068, Laboratoire de Synthèse et Physico-Chimie de Molécules d'Intérêt Biologique, 118, Route de Narbonne, F-31062 Toulouse Cedex 9, France; CNRS, UMR 5068, Laboratoire de Synthèse et Physico-Chimie de Molécules d'Intérêt Biologique, 118, Route de Narbonne, F-31062 Toulouse Cedex 9, France. Electronic address: bedos@chimie.ups-tlse.fr.
authors.forename: Florence
authors.initials: F
authors.lastname: Bedos-Belval
authors.affiliation: Université Paul Sabatier Toulouse III, UMR 5068, Laboratoire de Synthèse et Physico-Chimie de Molécules d'Intérêt Biologique, 118, Route de Narbonne, F-31062 Toulouse Cedex 9, France; CNRS, UMR 5068, Laboratoire de Synthèse et Physico-Chimie de Molécules d'Intérêt Biologique, 118, Route de Narbonne, F-31062 Toulouse Cedex 9, France. Electronic address: baltas@chimie.ups-tlse.fr.
authors.forename: Michel
authors.initials: M
authors.lastname: Baltas
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D042783:Endothelial Cells / Q000187:drug effects / Q000378:metabolism / Q000528:radiation effects; D006835:Hydrazones / Q000138:chemical synthesis / Q000737:chemistry*; D008077:Lipoproteins, LDL / Q000737:chemistry / Q000494:pharmacology; D051379:Mice; D010084:Oxidation-Reduction; D010636:Phenols / Q000737:chemistry; D020011:Protective Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D013329:Structure-Activity Relationship; D013481:Superoxides / Q000378:metabolism; D014466:Ultraviolet Rays
chemical_list: D000975:Antioxidants; D006835:Hydrazones; D008077:Lipoproteins, LDL; D010636:Phenols; D020011:Protective Agents; C099252:oxidized low density lipoprotein; D013481:Superoxides
keywords: Arylhydrazones; Atherosclerosis; LDL oxidation; Oxidative stress; Phenolic antioxidants