Amidoximes and Oximes: Synthesis, Structure, and Their Key Role as NO Donors.

Nitric oxide (NO) is naturally synthesized in the human body and presents many beneficial biological effects; in particular on the cardiovascular system. Recently; many researchers tried to develop external sources to increase the NO level in the body; for example by using amidoximes and oximes which can be oxidized in vivo and release NO. In this review; the classical methods and most recent advances for the synthesis of both amidoximes and oximes are presented first. The isomers of amidoximes and oximes and their stabilities will also be described; (Z)-amidoximes and (Z)-oximes being usually the most energetically favorable isomers. This manuscript details also the biomimetic and biological pathways involved in the oxidation of amidoximes and oximes. The key role played by cytochrome P450 or other dihydronicotinamide-adenine dinucleotide phosphate (NADPH)-dependent reductase pathways is demonstrated. Finally, amidoximes and oximes exhibit important effects on the relaxation of both aortic and tracheal rings alongside with other effects as the decrease of the arterial pressure and of the thrombi formation.

Synthesis of novel mono and bis nitric oxide donors with high cytocompatibility and release activity.

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.