Abstract
This review aims to clarify (1) what is a true mimic of superoxide dismutase family of enzymes, SOD; and (2) whether such compound could act as SOD mimic in a complex biological milieu. Several groups of compounds (metalloporphyrins, metallocorroles, Mn biliverdins, Mn cyclic polyamines, Mn salens, and metal oxides and salts) have been described. Their ability to catalyze the dismutation of O2·–, [kcat(O2·–)], thermodynamic property that supports high catalytic ability (E1/2), kinetic factors that facilitate the catalysis, and the stability of compounds, which assures the integrity of metal coordination sphere where reactions of interest occur have been discussed. The other possible in vivo actions of those compounds, such as peroxynitrite and hypochlorite reduction, peroxidase-like activity, thiol oxidase activity etc., have been described as well. Based on in vivo studies it appears that kcat(O2·–) for Mn(III) N-substituted pyridylporphyrins parallels their therapeutic ability. The reason for that lies in their electrophilic nature which favors reactions with nucleophilic (anionic) reactive species (O2·–, ONOO–, ClO–, HO2–, CO3·–) and simple or protein thiolates. Their in vivo multiple rather than single modes of actions, would be determined by: (a) their redox properties; (b) localization at targeted cellular site; and (c) redox environment of diseased or mutated/cancer cell. Quality of any drug preparation and the knowledge of researchers on its properties are essential when its mechanistic aspects are explored.
The authors are thankful to Duke University’s CTSA grant 1 UL 1 RR024128-01 from NCRR/NIH (AT, IBH, IS), W.H. Coulter Translational Partners Grant Program (IBH, IS, AT), the NIH/NCI Duke Comprehensive Cancer Center Core Grant (5-P30-CA14236-29) (IS), PK/PD DCI Shared Resources, and IBH general research funds (AT).
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Articles in the same Issue
- Cover and Frontmatter
- Editorial
- Special issue on Medicinal Redox Inorganic Chemistry
- Reviews
- Texaphyrins and water-soluble zinc(II) ionophores: development, mechanism of anticancer activity, and synergistic effects
- Macrophage activation by apoptotic cells
- The redox properties of the unique heme in cystathionine β-synthase
- The complex mechanistic aspects of redox-active compounds, commonly regarded as SOD mimics
- Short Communication
- Standard electrode potentials involving radicals in aqueous solution: inorganic radicals
- Abstracts
- MEDICINAL REDOX INORGANIC CHEMISTRY CONFERENCE 2013
Articles in the same Issue
- Cover and Frontmatter
- Editorial
- Special issue on Medicinal Redox Inorganic Chemistry
- Reviews
- Texaphyrins and water-soluble zinc(II) ionophores: development, mechanism of anticancer activity, and synergistic effects
- Macrophage activation by apoptotic cells
- The redox properties of the unique heme in cystathionine β-synthase
- The complex mechanistic aspects of redox-active compounds, commonly regarded as SOD mimics
- Short Communication
- Standard electrode potentials involving radicals in aqueous solution: inorganic radicals
- Abstracts
- MEDICINAL REDOX INORGANIC CHEMISTRY CONFERENCE 2013