Synthesis of novel mono and bis nitric oxide donors with high cytocompatibility and release activity.
Fiche publication
Date publication
septembre 2018
Journal
Bioorganic & medicinal chemistry letters
Auteurs
Membres identifiés du Cancéropôle Est :
Pr SCHNEIDER Raphaël, Dr ARRAULT Axelle
Tous les auteurs :
Sahyoun T, Gaucher C, Zhou Y, Ouaini N, Schneider R, Arrault A
Lien Pubmed
Résumé
Four compounds bearing amidoxime functions were synthetized: (1) 2a,b bearing an aromatic amidoxime function, (2) 2c bearing an aliphatic amidoxime function, and (3) 2d bearing aromatic and aliphatic amidoximes functions. The ability of these compounds to release NO was evaluated in vitro using the oxidative metabolism of cytochrome P450 from rat liver microsomes. Results obtained demonstrate that all amidoximes were able to release NO with a highest amount of NO produced by the 2a aromatic amidoxime. Moreover, all amidoximes exhibit cytocompatibility with human aorta smooth muscle cells. Using intracellular S-nitrosothiol formation as a marker of NO bioavailability, compounds 2a-c were demonstrated to deliver a higher amount of NO in the intracellular environment than the reference. Considering that the concentration of the bis-amidoxime 2d was two times lower that than of 2a and 2b, we can assume that 2d is the most potent molecule among the tested compounds for NO release.
Mots clés
Amidoximes, Cardiovascular disease, Double donor, Nitric oxide, Oxidation
Référence
Bioorg. Med. Chem. Lett.. 2018 Sep 8;: