Document Detail

Pure manganese(III) 5,10,15,20-tetrakis(4-benzoic acid)porphyrin (MnTBAP) is not a superoxide dismutase mimic in aqueous systems: a case of structure-activity relationship as a watchdog mechanism in experimental therapeutics and biology.
MedLine Citation:
PMID:  18046586     Owner:  NLM     Status:  MEDLINE    
Superoxide is involved in a plethora of pathological and physiological processes via oxidative stress and/or signal transduction pathways. Superoxide dismutase (SOD) mimics have, thus, been actively sought for clinical and mechanistic purposes. Manganese(III) 5,10,15,20-tetrakis(4-benzoic acid)porphyrin (MnTBAP) is one of the most intensely explored "SOD mimics" in biology and medicine. However, we show here that this claimed SOD activity of MnTBAP in aqueous media is not corroborated by comprehensive structure-activity relationship studies for a wide set of Mn porphyrins and that MnTBAP from usual commercial sources contains different amounts of noninnocent trace impurities (Mn clusters), which inhibited xanthine oxidase and had SOD activity in their own right. In addition, the preparation and thorough characterization of a high-purity MnTBAP is presented for the first time and confirmed that pure MnTBAP has no SOD activity in aqueous medium. These findings call for an assessment of the relevance and suitability of using MnTBAP (or its impurities) as a mechanistic probe and antioxidant therapeutic; conclusions on the physiological and pathological role of superoxide derived from studies using MnTBAP of uncertain purity should be examined judiciously. An unequivocal distinction between the biological effects due to MnTBAP and that of its impurities can only be unambiguously made if a pure sample is/was used. This work also illustrates the contribution of fundamental structure-activity relationship studies not only for drug design and optimization, but also as a "watchdog" mechanism for checking/spotting eventual incongruence of drug activity in chemical and biological settings.
Júlio S Rebouças; Ivan Spasojević; Ines Batinić-Haberle
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural     Date:  2007-11-29
Journal Detail:
Title:  Journal of biological inorganic chemistry : JBIC : a publication of the Society of Biological Inorganic Chemistry     Volume:  13     ISSN:  0949-8257     ISO Abbreviation:  J. Biol. Inorg. Chem.     Publication Date:  2008 Feb 
Date Detail:
Created Date:  2008-01-25     Completed Date:  2008-06-11     Revised Date:  2013-03-21    
Medline Journal Info:
Nlm Unique ID:  9616326     Medline TA:  J Biol Inorg Chem     Country:  Germany    
Other Details:
Languages:  eng     Pagination:  289-302     Citation Subset:  IM    
Department of Radiation Oncology, Duke University Medical School, Durham, NC 27710, USA.
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MeSH Terms
Cell Membrane / metabolism
Free Radical Scavengers / chemistry,  metabolism
Metalloporphyrins / chemical synthesis,  chemistry*,  metabolism*
Spectrometry, Mass, Electrospray Ionization
Spectrophotometry, Ultraviolet
Structure-Activity Relationship
Superoxide Dismutase*
Superoxides / metabolism
Grant Support
5-P30-CA14236-29/CA/NCI NIH HHS; IR21-ESO3682//PHS HHS; U19 AI067798/AI/NIAID NIH HHS; U19AI67798-01/AI/NIAID NIH HHS
Reg. No./Substance:
0/Free Radical Scavengers; 0/Metalloporphyrins; 0/manganese(III)-tetrakis(4-benzoic acid)porphyrin; 11062-77-4/Superoxides; 7732-18-5/Water; EC Dismutase

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