title: On the vasoprotective mechanisms underlying novel β-phosphorylated nitrones: Focus on free radical characterization, scavenging and NO-donation in a biological model of oxidative stress.
abstract: A series of new hybrid 2-(diethoxyphosphoryl)-N-(benzylidene)propan-2-amine oxide derivatives with different aromatic substitution (PPNs) were synthesized. These molecules were evaluated for their EPR spin trapping potential on eleven different radicals and NO-donation properties in vitro, cytotoxicity and vasoprotective effect on precontracted rat aortic rings. A subfamily of the new PPNs featured an antioxidant moiety occurring in natural phenolic acids. From the experimental screening of these hydroxyphenyl- and methoxyphenyl-substituted PPNs, biocompatible nitrones 4d, and 4g-4i deriving from caffeic, gallic, ferulic and sinapic acids, which combined improved EPR probing of ROS formation, vasorelaxant action and antioxidant potency, might be potential drug candidate alternatives to PBN and its analogues.
authors.affiliation: Aix Marseille Université, CNRS, UMR 7273, Institut de Chimie Radicalaire, Equipe Sondes Moléculaires en Biologie et Stress Oxydant (SMBSO), Service 522, 13397, Marseille, Cedex 20, France.
authors.forename: Mathieu
authors.initials: M
authors.lastname: Cassien
authors.affiliation: Aix Marseille Université, CNRS, UMR 7273, Institut de Chimie Radicalaire, Equipe Sondes Moléculaires en Biologie et Stress Oxydant (SMBSO), Service 522, 13397, Marseille, Cedex 20, France.
authors.forename: Consuelo
authors.initials: C
authors.lastname: Petrocchi
authors.affiliation: Aix Marseille Université, CNRS, UMR 7273, Institut de Chimie Radicalaire, Equipe Sondes Moléculaires en Biologie et Stress Oxydant (SMBSO), Service 522, 13397, Marseille, Cedex 20, France.
authors.forename: Sophie
authors.initials: S
authors.lastname: Thétiot-Laurent
authors.affiliation: Aix Marseille Université, CNRS, UMR 7273, Institut de Chimie Radicalaire, Equipe Sondes Moléculaires en Biologie et Stress Oxydant (SMBSO), Service 522, 13397, Marseille, Cedex 20, France.
authors.forename: Maxime
authors.initials: M
authors.lastname: Robin
authors.affiliation: Aix Marseille Université, CNRS, UMR 7273, Institut de Chimie Radicalaire, Equipe Sondes Moléculaires en Biologie et Stress Oxydant (SMBSO), Service 522, 13397, Marseille, Cedex 20, France.
authors.forename: Emilie
authors.initials: E
authors.lastname: Ricquebourg
authors.affiliation: Aix Marseille Université, CNRS, UMR 7273, Institut de Chimie Radicalaire, Equipe Sondes Moléculaires en Biologie et Stress Oxydant (SMBSO), Service 522, 13397, Marseille, Cedex 20, France.
authors.forename: Chouaib
authors.initials: C
authors.lastname: Kandouli
authors.affiliation: Aix Marseille Université, CNRS, UMR 7273, Institut de Chimie Radicalaire, Equipe Sondes Moléculaires en Biologie et Stress Oxydant (SMBSO), Service 522, 13397, Marseille, Cedex 20, France.
authors.forename: Alice
authors.initials: A
authors.lastname: Asteian
authors.affiliation: Aix Marseille Université, CNRS, UMR 7273, Institut de Chimie Radicalaire, Equipe Sondes Moléculaires en Biologie et Stress Oxydant (SMBSO), Service 522, 13397, Marseille, Cedex 20, France; Research Centre for Natural Sciences of the Hungarian Academy of Sciences, Institute of Materials and Environmental Chemistry, Budapest University of Technology and Economics, Hungary.
authors.forename: Antal
authors.initials: A
authors.lastname: Rockenbauer
authors.affiliation: Aix Marseille Université, CNRS, UMR 7273, Institut de Chimie Radicalaire, Equipe Sondes Moléculaires en Biologie et Stress Oxydant (SMBSO), Service 522, 13397, Marseille, Cedex 20, France.
authors.forename: Anne
authors.initials: A
authors.lastname: Mercier
authors.affiliation: Aix Marseille Université, CNRS, UMR 7273, Institut de Chimie Radicalaire, Equipe Sondes Moléculaires en Biologie et Stress Oxydant (SMBSO), Service 522, 13397, Marseille, Cedex 20, France.
authors.forename: Marcel
authors.initials: M
authors.lastname: Culcasi
authors.affiliation: Aix Marseille Université, CNRS, UMR 7273, Institut de Chimie Radicalaire, Equipe Sondes Moléculaires en Biologie et Stress Oxydant (SMBSO), Service 522, 13397, Marseille, Cedex 20, France. Electronic address: sylvia.pietri@univ-amu.fr.
authors.forename: Sylvia
authors.initials: S
authors.lastname: Pietri
mesh_terms: D000818:Animals; D001011:Aorta / Q000187:drug effects* / Q000502:physiology; D001713:Biphenyl Compounds / Q000737:chemistry; D002417:Cattle; D045744:Cell Line, Tumor; D016166:Free Radical Scavengers / Q000737:chemistry* / Q000494:pharmacology*; D005609:Free Radicals / Q000737:chemistry; D057927:Hydrophobic and Hydrophilic Interactions; D009569:Nitric Oxide / Q000737:chemistry* / Q000378:metabolism; D009589:Nitrogen Oxides / Q000737:chemistry* / Q000494:pharmacology*; D018384:Oxidative Stress / Q000187:drug effects*; D010766:Phosphorylation; D010851:Picrates / Q000737:chemistry; D050050:Protein Carbonylation / Q000187:drug effects; D051381:Rats; D019097:Spin Trapping; D013481:Superoxides / Q000737:chemistry; D014664:Vasodilation / Q000187:drug effects
chemical_list: D001713:Biphenyl Compounds; D016166:Free Radical Scavengers; D005609:Free Radicals; D009589:Nitrogen Oxides; D010851:Picrates; C015388:nitrones; D013481:Superoxides; D009569:Nitric Oxide; C004931:1,1-diphenyl-2-picrylhydrazyl
keywords: Antioxidant; Aortic rings relaxation; EPR spin trapping; NO donors; Phenolic acids; β-Diethoxyphosphoryl nitrones