氮氧自由基捕获剂的化学性质和生物活性对治疗的潜在影响。
Potential implication of the chemical properties and bioactivity of nitrone spin traps for therapeutics.
机构信息
Department of Pharmacology, & Davis Heart & Lung Research Institute, College of Medicine, The Ohio State University, Columbus, OH 43210, USA.
出版信息
Future Med Chem. 2012 Jun;4(9):1171-207. doi: 10.4155/fmc.12.74.
Abstract
Nitrone therapeutics has been employed in the treatment of oxidative stress-related diseases such as neurodegeneration, cardiovascular disease and cancer. The nitrone-based compound NXY-059, which is the first drug to reach clinical trials for the treatment of acute ischemic stroke, has provided promise for the development of more robust pharmacological agents. However, the specific mechanism of nitrone bioactivity remains unclear. In this review, we present a variety of nitrone chemistry and biological activity that could be implicated for the nitrone's pharmacological activity. The chemistries of spin trapping and spin adduct reveal insights on the possible roles of nitrones for altering cellular redox status through radical scavenging or nitric oxide donation, and their biological effects are presented. An interdisciplinary approach towards the development of novel synthetic antioxidants with improved pharmacological properties encompassing theoretical, synthetic, biochemical and in vitro/in vivo studies is covered.
摘要
硝酮治疗学已被应用于治疗与氧化应激相关的疾病，如神经退行性疾病、心血管疾病和癌症。基于硝酮的化合物 NXY-059 是第一种用于治疗急性缺血性中风的临床试验药物，为开发更强大的药理学药物提供了希望。然而，硝酮生物活性的具体机制仍不清楚。在这篇综述中，我们介绍了各种硝酮化学和生物学活性，这些活性可能与硝酮的药理学活性有关。自旋捕获和自旋加合物的化学揭示了硝酮通过清除自由基或捐赠一氧化氮来改变细胞氧化还原状态的可能作用，以及它们的生物学效应。涵盖了一种跨学科的方法，用于开发具有改善的药理学性质的新型合成抗氧化剂，包括理论、合成、生化以及体外/体内研究。
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