NO Donor Drugs: Chemical Synthesis And Biological Actions

NO is involved in many physiology and pathological process. NO donor drugs that directly or indirectly release NO are used in the treatment of cardiovascular diseases, neurological and cancer. Several new NO donor drugs that directly or indirectly release NO have been designed and prepared in order to provide a theoretical basis for further experiments.Two kinds of S-Nitrosothiols, S-nitroso-ethyl-thioglycolate (a) and S-nitroso-thioglycol (b), were synthesized by nitrosation.N-nitroso folic acid (c) was prepared by attaching the NO group to the number 10 N atom of the folic acid. The structures of the three NO donor drugs were characterized by UV-vis, IR, MS and 1HNMR. The nitric oxide released processes of the three NO donor drugs were detected by the N-(1-naphthyl)-ethylenediamine dihydrochloride spectrophotometric mthod and the chemiluminescent method.The results showed that the order of the NO released efficiency was: a> b> c. The three NO donor drugs were prepared at different concentrations: 1.0×10^-4 mol/L, 5.0×10^-4 mol/L, 1.0×10^-3 mol/L, and 5.0×10^-3 mol/L for determination their functions,scavenging O2-, OH·, H2O2 and anti-lipid peroxidation. All showed that they could scavenge O2-, H2O2, OH·and have obvious action of decreasing the lipid peroxidation. To investigate the relaxation of the three NO donor drugs on isolated aorta pectoralis circle of the rabbit and systolic blood pressure (SBP), diastolic blood pressure (DBP) and heart rates (HR) of the rats with multi-channel signal acquisition system. All showed that they could relaxe isolated aorta pectoralis circle of the rabbit and decrease blood pressure of the rats.