CIQUP/Departamento de Química e Bioquímica, Faculdade de Ciências, Universidade do Porto, Porto, Portugal.
Med Res Rev. 2018 Jul;38(4):1159-1187. doi: 10.1002/med.21461. Epub 2017 Nov 2.
The biological effects attributed to nitric oxide ( NO) and nitroxyl (HNO) have been extensively studied, propelling their array of putative clinical applications beyond cardiovascular disorders toward other age-related diseases, like cancer and neurodegenerative diseases. In this context, the unique properties and reactivity of the N-O bond enabled the development of several classes of compounds with potential clinical interest, among which NO and HNO donors, nitrones, and nitroxides are of particular importance. Although primarily studied for their application as cardioprotective agents and/or molecular probes for radical detection, continuous efforts have unveiled a wide range of pharmacological activities and, ultimately, therapeutic applications. These efforts are of particular significance for diseases in which oxidative stress plays a key pathogenic role, as shown by a growing volume of in vitro and in vivo preclinical data. Although in its early stages, these efforts may provide valuable guidelines for the development of new and effective N-O-based drugs for age-related disorders. In this report, we review recent advances in the chemistry of NO and HNO donors, nitrones, and nitroxides and discuss its pharmacological significance and potential therapeutic application.
一氧化氮（NO）和亚硝酰（HNO）的生物学效应已经得到了广泛的研究，这推动了它们在心血管疾病以外的一系列潜在临床应用，如癌症和神经退行性疾病。在这种情况下，N-O 键的独特性质和反应性使得开发了具有潜在临床意义的几类化合物，其中 NO 和 HNO 供体、硝酮和氮氧自由基特别重要。尽管它们主要作为心脏保护剂和/或自由基检测的分子探针进行研究，但不断的努力揭示了广泛的药理学活性，并最终带来了治疗应用。这些努力对于氧化应激在其中发挥关键致病作用的疾病尤其重要，这一点已经有大量的体外和体内临床前数据得到了证实。尽管还处于早期阶段，但这些努力可能为开发针对与年龄相关的疾病的新型有效的基于 N-O 的药物提供有价值的指导。在本报告中，我们综述了 NO 和 HNO 供体、硝酮和氮氧自由基的化学进展，并讨论了它们的药理学意义和潜在的治疗应用。
