2. Academic Validation
  3. 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

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

  • Eur J Med Chem. 2016 Aug 25:119:197-217. doi: 10.1016/j.ejmech.2016.04.067.
Mathieu Cassien 1,  Consuelo Petrocchi 1,  Sophie Thétiot-Laurent 1,  Maxime Robin 1,  Emilie Ricquebourg 1,  Chouaib Kandouli 1,  Alice Asteian 1,  Antal Rockenbauer 2,  Anne Mercier 1,  Marcel Culcasi 1,  Sylvia Pietri 3
Affiliations

Affiliations

  • 1 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.
  • 2 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.
  • 3 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.
PMID: 27162124 DOI: 10.1016/j.ejmech.2016.04.067
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.

Keywords

Antioxidant; Aortic rings relaxation; EPR spin trapping; NO donors; Phenolic acids; β-Diethoxyphosphoryl nitrones.

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