Synthesis and Characterization of Biologically Active NO-donors

一氧化氮（Nitric oxide，NO）是一种重要的生物调节分子，参与巨噬细胞的活动和内皮细胞的舒张功能，但由于NO是一种气态的、不稳定的物质，其生物学效应的研究难以进行。我们已经开发了一种在生物条件下释放NO的化合物，该化合物可用于NO.N-亚硝基化合物是通过相应的脲或酰胺的亚硝化反应制备的。本文报道了用N^3 -二烷基苯基脲与亚硝酸钠在甲酸中反应得到三取代亚硝基脲，再与亚硝酸异戊酯在氯仿中亚硝化得到二取代亚硝基脲。用Griess-Salzman法测定了N-亚硝基化合物的NO生成量。生成的NO在Griess试剂中在氧气存在下转化为NO_2-，然后在Na_2SO_4中还原为NO_2-，再在Na_2SO_4中还原为NO_2-，最后在Na_2SO_4中还原为NO_2-，再在Na_2SO_4中还原为NO_2-，最后在Na_2SO_4中还原为NO ...更多信息 N-亚硝基脲的脲基-N^3氮上烷基取代基的大小影响NO的生成能力，当脲基-N^1氮上的孤对电子与芳环上的π电子共轭时，N-NO键变得易受影响并均质断裂以产生NO。不具有这种共轭体系的脂肪族N-亚硝基化合物在我们的实验条件下永远不会产生NO。3，3-二苄基-1-（4-甲苯基）-1-亚硝基脲在室温下产生NO的能力最强，用L-5178 Y细胞进行的N-亚硝基化合物细胞毒试验表明，芳香族N-亚硝基化合物对L-5178 Y细胞的生长抑制具有明显的细胞毒作用。NO的生成量与N-亚硝基化合物的ID_（50）值的倒数有关，表明N-亚硝基脲类化合物是具有生物活性的NO供体，在生物条件下可以释放NO。少

Nitric oxide (NO) is an important bioregulatory molecule responsible for endothelium-derived relaxation and to be involved in the actions of macrophages.However, the difficulty in handling such a gaseous and labile NO causes problems with the effective and precise studies of the biological effects of NO.In these situations, we have developed an NO-releasing compound under biological conditions that is useful for the chemical and biochemical research of the action of NO.N-Nitroso compounds were prepared by the nitrosation of the corresponding ureas or amides. Trisubstituted nitrosoureas were obtained by the reaction with N^3 -dialkylated phenylureas and sodium nitrite in formic acid.Disubstituted nitrosoureas were prepared by the nitrosation with isoamyl nitrite in chloroform.The Griess-Salzman method was applied to determine the NO generation from the N-nitroso compounds.The generated NO was changed to NO_2- in the solution of the Griess reagent in the presence of oxygen and subsequent … More ly converted to an azo compound.The synthesized N-nitroso compounds release NO and the sizes of the alkyl substituents at the ureido-N^3 nitrogen of the N-nitrosoureas influenced the ability of NO generation.When the lone pair electrons on the ureide-N^1 nitrogen conjugate with pi-electrons on the aromatic ring, the N-NO bond becomes liable and is homolitically cleaved to generate NO.Aliphatic N-nitroso compounds not having such a conjugated system could never yield NO in our experimental conditions.3,3-Dibenzyl-l-(4-tolyl)-1-nitrosourea had the best NO generating ability at room temperature.The cytotoxic tests of N-nitroso compounds using cultured L-5178 Y cells revealed that the cytotoxic action of the aromatic N-nitroso compounds on the growth inhibition was apparently good. The amount of NO genration was related to the reciprocal of the ID50 values for the N-nitroso compounds.It is revealed that N-nitrosoureas are good candidates for the biologically active NO-donors which can release in the biological conditions. Less