L'article "Synthesis of novel mono and bis nitric oxide donors with high cytocompatibility and release activity" vient de paraître dans le journal "Bioorganic & Medicinal Chemistry Letters"
Auteurs : Tanya Sahyoun, Caroline Gaucher, Yi Zhou, Naïm Ouaini, Raphaël Schneider and Axelle Arrault
Référence de l'article : Bioorganic & Medicinal Chemistry Letters, DOI: 110.1016/j.bmcl.2018.09.009
Highlights
•A series of aromatic and aliphatic mono-amidoximes and bis-amidoximes were synthesized.
•Amodoximes were tested for their NO release ability on rat liver microsomes and human vascular cells.
•Amidoximes are cytocompatible with human vascular smooth muscle cells.
•Mono-amidoximes 2a and 2b exhibit high NO release.
•Bis-amidoxime 2d releases the same amount of NO than 2a and 2b at a twice lower concentration.
Abstract :
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.
