Simple biological systems for assessing the activity of superoxide dismutase mimics.
Simple biological systems for assessing the activity of superoxide dismutase mimics.
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用于评估超氧化物歧化酶模拟物活性的简单生物系统。
DOI：
10.1089/ars.2013.5576
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发表时间：
2014
影响因子：
6.6
通讯作者：
Benov,Ludmil
中科院分区：
文献类型：
--
作者：
Tovmasyan,Artak;Reboucas,JulioS;Benov,Ludmil
意义：半个世纪的研究提供了明确的证据表明，超氧化物和来自它的物种-活性氧（ROS）-在许多疾病和退行性过程中发挥着核心作用。这刺激了对能够预防氧化损伤的药剂以及评估其治疗潜力的方法的研究。最近的进展：超氧化物歧化酶（SOD）作为治疗工具的局限性将注意力转向能够催化清除超氧化物的小分子，SOD模拟物。已经开发了几组基于金属络合物的化合物，包括金属卟啉、金属吡咯、Mn（II）环状多胺和Mn（III）salen衍生物，或基于非金属的化合物，如富勒烯、硝酮和氮氧化物，并在体外和体内进行了研究。关键问题和未来方向：SOD模拟物的发展需要深入了解其生物学作用机制。阐明这两个分子特征，有效的ROS清除体内必不可少的，和限制潜在的副作用的因素，需要生物学相关的，在同一时间，相对简单的测试系统。本文综述了基因工程SOD缺陷型单细胞生物、大肠杆菌和酵母作为研究SOD模拟物生物学作用的有效性和机制的工具的优点和局限性。这些简单的系统允许审查的最低要求的功能SOD模拟：协会的高催化活性的超氧化物歧化，低毒性，和有效的细胞摄取/生物分布。抗氧化剂。Redox Signal.20，2416-2436.
Significance:Half a century of research provided unambiguous proof that superoxide and species derived from it—reactive oxygen species (ROS)—play a central role in many diseases and degenerative processes. This stimulated the search for pharmaceutical agents that are capable of preventing oxidative damage, and methods of assessing their therapeutic potential.Recent Advances:The limitations of superoxide dismutase (SOD) as a therapeutic tool directed attention to small molecules, SOD mimics, that are capable of catalytically scavenging superoxide. Several groups of compounds, based on either metal complexes, including metalloporphyrins, metallocorroles, Mn(II) cyclic polyamines, and Mn(III) salen derivatives, or non-metal based compounds, such as fullerenes, nitrones, and nitroxides, have been developed and studiedin vitroandin vivo. Very few entered clinical trials.Critical Issues and Future Directions:Development of SOD mimics requires in-depth understanding of their mechanisms of biological action. Elucidation of both molecular features, essential for efficient ROS-scavengingin vivo, and factors limiting the potential side effects requires biologically relevant and, at the same time, relatively simple testing systems. This review discuses the advantages and limitations of genetically engineered SOD-deficient unicellular organisms,Escherichia coliandSaccharomyces cerevisiaeas tools for investigating the efficacy and mechanisms of biological actions of SOD mimics. These simple systems allow the scrutiny of the minimal requirements for a functional SOD mimic: the association of a high catalytic activity for superoxide dismutation, low toxicity, and an efficient cellular uptake/biodistribution.Antioxid. Redox Signal.20, 2416–2436.