[NO-release ability and DNA-damage activity of aromatic N-nitroso compounds]

To develop a new nitric oxide-donor (NO-donor) that is useful for chemical and biochemical research, we synthesized several aromatic N-nitroso compounds including 1-[N-nitroso-N-(4-tolyl)carbamoyl] piperidine-4-carboxylic acid (1f) and phenyl(2-pyridyl)-N-nitrosamines, which spontaneously generate NO at ambient temperature. Thermal decomposition of these compounds was run under mild conditions. Gaseous NO released from them was quantified by means of the Griess reaction using a specially designed apparatus in which NO2- is generated from NO. The structure of products arose from the radical cleavage of N-NO bond was clarified by chemical and spectral studies. Generation of NO from the N-nitroso compounds was also confirmed by ESR spectroscopy. The action of these NO-releasing compounds against DNA was examined. When the pBR 322 DNA was treated with 1f at 37 degrees C for 3 h, the DNA single-strand breaks was 31% for 1 mM of 1f. The denitrosated compound and sodium nitrite did not show any effective DNA-cleaving activity. On the other hand, aromatic N-nitrosamines induced weak DNA-cleaving activity under the same condition.