Tanno Masayuki, Sueyoshi Shoko, Fukuhara Kiyoshi, Miyata Naoki, Okuda Haruhiro
Kokuritsu Iyakuhin Shokuhin Eisei Kenkyusho Hokoku. 2004(122):10-5.
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.
为开发一种可用于化学和生化研究的新型一氧化氮供体（NO供体），我们合成了几种芳香族N-亚硝基化合物，包括1-[N-亚硝基-N-(4-甲苯基)氨基甲酰基]哌啶-4-羧酸（1f）和苯基(2-吡啶基)-N-亚硝基胺，它们在室温下能自发产生NO。这些化合物的热分解在温和条件下进行。使用专门设计的装置通过格里斯反应对它们释放的气态NO进行定量，该装置可使NO生成NO2-。通过化学和光谱研究阐明了由N-NO键自由基裂解产生的产物结构。ESR光谱也证实了这些N-亚硝基化合物能产生NO。研究了这些释放NO的化合物对DNA的作用。当pBR 322 DNA在37℃下用1f处理3小时时，对于1 mM的1f，DNA单链断裂率为31%。脱亚硝基化产物和亚硝酸钠未显示出任何有效的DNA切割活性。另一方面，芳香族N-亚硝基胺在相同条件下诱导出较弱的DNA切割活性。
