title: Simple biological systems for assessing the activity of superoxide dismutase mimics.
abstract: CONCLUSIONS
  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.
  
  
  BACKGROUND
  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 studied in vitro and in vivo. Very few entered clinical trials.
  
  
  CONCLUSIONS
  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 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 coli and Saccharomyces cerevisiae as 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.
authors: 1 Department of Radiation Oncology, Duke University Medical Center , Durham, North Carolina.
authors: Artak
authors: A
authors: Tovmasyan
authors: Julio S
authors: JS
authors: Reboucas
authors: Ludmil
authors: L
authors: Benov
mesh_terms: D000818:Animals; D002384:Catalysis; D004789:Enzyme Activation; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D008665:Metalloporphyrins / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D018716:Molecular Mimicry; D009154:Mutation; D013482:Superoxide Dismutase / Q000737:chemistry / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology*
chemical_list: D008665:Metalloporphyrins; D013482:Superoxide Dismutase
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