On the vasoprotective mechanisms underlying novel beta-phosphorylated nitrones: Focus on free radical characterization, scavenging and NO-donation in a biological model of oxidative stress

Mathieu Cassien (1) , Petrocchi Consuelo (1) , Sophie Thétiot-Laurent (1) , Maxime Robin (1) , Ricquebourg Emilie (1) , Kandouli Chouaib (1) , Alice Asteian (1) , Antal Rockenbauer (1, 2) , Anne Mercier (1) , Marcel Culcasi (1) , Sylvia Pietri (1)

1 ICR - Institut de Chimie Radicalaire
2 Chemical Research Center, Institute of Chemistry, Budapest

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: beta-Diethoxyphosphoryl nitrones; Aortic rings relaxation; Phenolic acids; Antioxidant; NO donors; EPR spin trapping

Domains: Chemical Sciences; Medicinal Chemistry; Chemical Sciences; Organic chemistry

Mathieu Cassien, Petrocchi Consuelo, Sophie Thétiot-Laurent, Maxime Robin, Ricquebourg Emilie, et al.. On the vasoprotective mechanisms underlying novel beta-phosphorylated nitrones: Focus on free radical characterization, scavenging and NO-donation in a biological model of oxidative stress. European Journal of Medicinal Chemistry, 2016, 119, pp.197-217. ⟨10.1016/j.ejmech.2016.04.067⟩. ⟨hal-01322596⟩