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首页> 外文期刊>Current topics in medicinal chemistry >N-hydroxyurea and acyl nitroso compounds as nitroxyl (HNO) and nitric oxide (NO) donors.
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N-hydroxyurea and acyl nitroso compounds as nitroxyl (HNO) and nitric oxide (NO) donors.

机译：N-羟基脲和酰基亚硝基化合物作为硝酰基（HNO）和一氧化氮（NO）供体。

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Hydroxyurea has emerged as a new therapy for sickle cell disease but a complete mechanistic description of its beneficial actions does not exist. Patients taking hydroxyurea show evidence for the in vivo conversion of hydroxyurea to nitric oxide (NO), which also has drawn interest as a sickle cell disease treatment. While the chemical oxidation of hydroxyurea produces NO or NO-related products, NO formation from the reactions of hydroxyurea and hemoglobin do not occur fast enough to account for the observed increases in patients taking hydroxyurea. Both horseradish peroxidase and catalase catalyze the rapid formation of nitric oxide and nitroxyl (HNO) from hydroxyurea. In these reactions, hydroxyurea is converted to an acyl nitroso species that hydrolyzes to form HNO. The ferric heme protein then oxidizes HNO to NO that combines with the heme iron to form a ferrous-NO complex that may act as an NO donor. In general, acyl nitroso compounds, regardless of the method of their preparation, hydrolyze to form HNO and the corresponding carboxylic acid derivative. Similarly, the incubation of blood and hydroxyurea with urease rapidly form NO-related species suggesting the initial urease-mediated hydrolysis of hydroxyurea to hydroxylamine, which then reacts quickly with hemoglobin to form these products. These studies present two NO releasing mechanisms from hydroxyurea that are kinetically competent with clinical observations.
机译：羟基脲已成为镰状细胞疾病的一种新疗法，但尚不存在对其有益作用的完整机理描述。服用羟基脲的患者显示出羟基脲体内转化为一氧化氮（NO）的证据，这也引起了镰状细胞疾病治疗的兴趣。尽管羟基脲的化学氧化产生NO或与NO相关的产物，但羟基脲和血红蛋白反应形成的NO生成的速度不足以解释服用羟基脲的患者中观察到的增加。辣根过氧化物酶和过氧化氢酶都催化从羟基脲中迅速形成一氧化氮和硝酰（HNO）。在这些反应中，羟基脲被转化为水解成HNO的酰基亚硝基。然后，血红素铁蛋白将HNO氧化为NO，并与血红素铁结合形成亚铁-NO络合物，可充当NO供体。通常，不管其制备方法如何，酰基亚硝基化合物都会水解形成HNO和相应的羧酸衍生物。类似地，血液和羟基脲与脲酶的温育迅速形成了与NO相关的物种，表明最初的脲酶介导的羟基脲水解为羟胺，然后与血红蛋白迅速反应形成这些产物。这些研究提出了从羟基脲释放NO的两种机制，这些机制在动力学上与临床观察相符。

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