Tovmasyan A, et al. (2013) Simple biological systems for assessing the activity of SOD mimics. Antioxid Redox Signal ()
Abstract: Significance: Half a century of research provided unambiguous proof that superoxide and species derived from it (ROS) play a central role in many diseases and degenerative processes. This stimulated the search for pharmaceutical agents capable of preventing oxidative damage, and methods to assess their therapeutic potential. Recent Advances: The limitations of superoxide dismutase (SOD) as a therapeutic tool directed attention to small molecules, SOD mimics, capable of catalytically scavenging superoxide. Several groups of compounds, based either on metal complexes, including metalloporphyrins, metallocorroles, Mn(II) cyclic polyamines, Mn(III) salen derivatives, or non-metal based compounds such as fullerenes, nitrones, and nitroxides, have been developed and studied in vitro and in 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-scavenging in vivo, and factors limiting potential side effects requires biologically relevant and at the same time, relatively simple testing systems. This review discuses advantages and limitations of genetically engineered SOD-deficient unicellular organisms, Escherichia coli and Saccharomyces cerevisiae as tools for investigating the efficacy and mechanisms of biological action 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.
|Status: Epub ahead of print||Type: Journal Article||PubMed ID: 23964890|
Topics addressed in this paper
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