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

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, cytotoxic...

Full description

Saved in:

Bibliographic Details
Published in:	European journal of medicinal chemistry Vol. 119; pp. 197 - 217
Main Authors:	Cassien, Mathieu, Petrocchi, Consuelo, Thétiot-Laurent, Sophie, Robin, Maxime, Ricquebourg, Emilie, Kandouli, Chouaib, Asteian, Alice, Rockenbauer, Antal, Mercier, Anne, Culcasi, Marcel, Pietri, Sylvia
Format:	Journal Article
Language:	English
Published:	France Elsevier Masson SAS 25-08-2016 Elsevier
Subjects:	Animals Antioxidant Aorta - drug effects Aorta - physiology Aortic rings relaxation Biphenyl Compounds - chemistry Cattle Cell Line, Tumor Chemical Sciences EPR spin trapping Free Radical Scavengers - chemistry Free Radical Scavengers - pharmacology Free Radicals - chemistry Hydrophobic and Hydrophilic Interactions Medicinal Chemistry Nitric Oxide - chemistry Nitric Oxide - metabolism Nitrogen Oxides - chemistry Nitrogen Oxides - pharmacology NO donors Organic chemistry Oxidative Stress - drug effects Phenolic acids Phosphorylation Picrates - chemistry Protein Carbonylation - drug effects Rats Spin Trapping Superoxides - chemistry Vasodilation - drug effects β-Diethoxyphosphoryl nitrones Aortic rings relaxation β-Diethoxyphosphoryl nitrones Antioxidant EPR spin trapping Phenolic acids NO donors beta-Diethoxyphosphoryl nitrones
Online Access:	Get full text
Tags:	Add Tag No Tags, Be the first to tag this record!

Description
Summary:	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. [Display omitted] •Phosphorylated nitrones bearing an antioxidant phenolic framework are synthesized.•EPR spin trapping, antioxidant and NO-donation properties are determined.•Biochemical indices and vasoconstriction are improved in stressed aortic rings.•Some new hybrid nitrones could be better drug candidates than PBN.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	0223-5234 1768-3254
DOI:	10.1016/j.ejmech.2016.04.067