Evaluation of the compounds commonly known as superoxide dismutase and catalase mimics in cellular models.
Abstract
Oxidative stress that results from an imbalance between the concentrations of reactive
species (RS) and antioxidant defenses is associated with many pathologies. Superoxide
dismutase (SOD), catalase (CAT), and glutathione peroxidase are among the key enzymes
that maintain the low nanomolar physiological concentrations of superoxide and hydrogen
peroxide. The increase in the levels of these species and their progeny could have
deleterious effects. In this context, chemists have developed SOD and CAT mimics to
supplement them when cells are overwhelmed with oxidative stress. However, the beneficial
activity of such molecules in cells depends not only on their intrinsic catalytic
activities but also on their stability in biological context, their cell penetration
and their cellular localization. We have employed cellular assays to characterize
several compounds that possess SOD and CAT activities and have been frequently used
in cellular and animal models. We used cellular assays that address SOD and CAT activities
of the compounds. Finally, we determined the effect of compounds on the suppression
of the inflammation in HT29-MD2 cells challenged by lipopolysaccharide. When the assay
requires penetration inside cells, the SOD mimics Mn(III) meso-tetrakis(N-(2'-n-butoxyethyl)pyridinium-2-yl)porphyrin
(MnTnBuOE-2-PyP5+) and Mn(II) dichloro[(4aR,13aR,17aR,21aR)-1,2,3,4,4a,5,6,12,13,13a,14,15,16,17,17a,18,19,20,21,21a-eicosahydro-11,7-nitrilo-7Hdibenzo[b,h]
[1,4, 7,10] tetraazacycloheptadecine-κN5,κN13,κN18,κN21,κN22] (Imisopasem manganese,
M40403, CG4419) were found efficacious at 10 μM, while Mn(II) chloro N-(phenolato)-N,N'-bis[2-(N-methyl-imidazolyl)methyl]-ethane-1,2-diamine
(Mn1) requires an incubation at 100 μM. This study thus demonstrates that MnTnBuOE-2-PyP5+, M40403 and Mn1 were efficacious in suppressing inflammatory response in HT29-MD2
cells and such action appears to be related to their ability to enter the cells and
modulate reactive oxygen species (ROS) levels.
Type
Journal articleSubject
AntioxidantCatalase mimic
Cellular assay
Oxidative stress
Reactive oxygen species
Superoxide dismutase mimic
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https://hdl.handle.net/10161/22717Published Version (Please cite this version)
10.1016/j.jinorgbio.2021.111431Publication Info
Vincent, Amandine; Thauvin, Marion; Quévrain, Elodie; Mathieu, Emilie; Layani, Sarah;
Seksik, Philippe; ... Delsuc, Nicolas (2021). Evaluation of the compounds commonly known as superoxide dismutase and catalase mimics
in cellular models. Journal of inorganic biochemistry, 219. pp. 111431. 10.1016/j.jinorgbio.2021.111431. Retrieved from https://hdl.handle.net/10161/22717.This is constructed from limited available data and may be imprecise. To cite this
article, please review & use the official citation provided by the journal.
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Show full item recordScholars@Duke
Ines Batinic-Haberle
Professor Emeritus of Radiation Oncology
A major interest of mine has been in the design and synthesis of Mn porphyrin(MnP)-based
powerful catalytic antioxidants which helped establish structure-activity relationship
(SAR). It relates the redox property of metalloporphyrins to their ability to remove
superoxide. SAR has facilitated the design of redox-active therapeutics and served
as a tool for mechanistic considerations. Importantly SAR parallels the magnitu

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