Orally available Mn porphyrins with superoxide dismutase and catalase activities

Rosenthal, Robert W.; Huffman, Karl; Fisette, Leslie; Damphousse, Christy A.; Callaway, Wyeth; Malfroy, Bernard; Doctrow, Susan R.

doi:10.1007/s00775-009-0550-4

Cited by 63 publications

(78 citation statements)

References 54 publications

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“…Unlike Dr. Batinić-Haberle, we believe that SOD activity is not as important as other properties, such as catalase and other reactive oxygen species or reactive nitrogen species scavenging properties, lipophilicity, lack of toxicity, or intracellular stability, in determining biological efficacy (discussed in our article) (2). Our position is further supported by our finding that these neutral Mn porphyrins are potently antiapoptotic in two cellular injury models (2,4), an important point that Dr. Batinić-Haberle et al fail to mention.…”

supporting

confidence: 62%

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Superoxide Dismutase Mimics

Rosenthal

Doctrow

Callaway³

2011

Antioxidants & Redox Signaling

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supporting

confidence: 62%

“…On page 888, in a section entitled Neutral Porphyrins, our research describing a series of such compounds is cited (2). The review states ''Yet, critical analytical data, such as elemental analysis, were again not provided.''…”

mentioning

confidence: 99%

Superoxide Dismutase Mimics

Rosenthal

Doctrow

Callaway³

2011

Antioxidants & Redox Signaling

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“…Another group of neutral porphyrins was reported recently by Rosenthal et al (272). Yet, critical analytical data, such as elemental analyses, were again not provided.…”

Section: Electrostaticsmentioning

confidence: 99%

Superoxide Dismutase Mimics: Chemistry, Pharmacology, and Therapeutic Potential

Batinić‐Haberle

Rebouças

Spasojević

2010

Antioxidants & Redox Signaling

471

689

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Oxidative stress has become widely viewed as an underlying condition in a number of diseases, such as ischemia-reperfusion disorders, central nervous system disorders, cardiovascular conditions, cancer, and diabetes. Thus, natural and synthetic antioxidants have been actively sought. Superoxide dismutase is a first line of defense against oxidative stress under physiological and pathological conditions. Therefore, the development of therapeutics aimed at mimicking superoxide dismutase was a natural maneuver. Metalloporphyrins, as well as Mn cyclic polyamines, Mn salen derivatives and nitroxides were all originally developed as SOD mimics. The same thermodynamic and electrostatic properties that make them potent SOD mimics may allow them to reduce other reactive species such as peroxynitrite, peroxynitrite-derived CO 3 _ À , peroxyl radical, and less efficiently H 2 O 2 . By doing so SOD mimics can decrease both primary and secondary oxidative events, the latter arising from the inhibition of cellular transcriptional activity. To better judge the therapeutic potential and the advantage of one over the other type of compound, comparative studies of different classes of drugs in the same cellular and=or animal models are needed. We here provide a comprehensive overview of the chemical properties and some in vivo effects observed with various classes of compounds with a special emphasis on porphyrin-based compounds. Antioxid. Redox Signal. 13, 877-918.

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“…No positive results were reported for M40403 (85). Since all these compounds are redox active, they most probably act by mechanisms other than catalysis of O 2 -dismutation (17,82,104).…”

Section: The Purity Of the Tested Compoundsmentioning

confidence: 99%

Simple Biological Systems for Assessing the Activity of Superoxide Dismutase Mimics

Tovmasyan

Rebouças

Benov

2014

Antioxidants & Redox Signaling

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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 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 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. Antioxid. Redox Signal. 20, 2416Signal. 20, -2436

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Orally available Mn porphyrins with superoxide dismutase and catalase activities

Cited by 63 publications

References 54 publications

Superoxide Dismutase Mimics

Superoxide Dismutase Mimics

Superoxide Dismutase Mimics: Chemistry, Pharmacology, and Therapeutic Potential

Simple Biological Systems for Assessing the Activity of Superoxide Dismutase Mimics

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