Organoselenium compounds as mimics of selenoproteins and thiol modifier agents

Nilda V. Barbosa, Cristina W. Nogueira, Pablo A. Nogara, Andreza F. De Bem, Michael Aschner, João B.T. Rocha

Research output: Contribution to journalReview article

25 Citations (Scopus)

Abstract

Selenium is an essential trace element for animals and its role in the chemistry of life relies on a unique functional group: the selenol (-SeH) group. The selenol group participates in critical redox reactions. The antioxidant enzymes glutathione peroxidase (GPx) and thioredoxin reductase (TrxR) exemplify important selenoproteins. The selenol group shares several chemical properties with the thiol group (-SH), but it is much more reactive than the sulfur analogue. The substitution of S by Se has been exploited in organic synthesis for a long time, but in the last 4 decades the re-discovery of ebselen (2-phenyl-1,2-benzisoselenazol-3(2H)-one) and the demonstration that it has antioxidant and therapeutic properties has renovated interest in the field. The ability of ebselen to mimic the reaction catalyzed by GPx has been viewed as the most important molecular mechanism of action of this class of compound. The term GPx-like or thiol peroxidase-like reaction was previously coined in the field and it is now accepted as the most important chemical attribute of organoselenium compounds. Here, we will critically review the literature on the capacity of organoselenium compounds to mimic selenoproteins (particularly GPx) and discuss some of the bottlenecks in the field. Although the GPx-like activity of organoselenium compounds contributes to their pharmacological effects, the superestimation of the GPx-like activity has to be questioned. The ability of these compounds to oxidize the thiol groups of proteins (the thiol modifier effects of organoselenium compounds) and to spare selenoproteins from inactivation by soft-electrophiles (MeHg+, Hg2+, Cd2+, etc.) might be more relevant for the explanation of their pharmacological effects than their GPx-like activity. In our view, the exploitation of the thiol modifier properties of organoselenium compounds can be harnessed more rationally than the use of low mass molecular structures to mimic the activity of high mass macromolecules that have been shaped by millions to billions of years of evolution.

Original languageEnglish (US)
Pages (from-to)1703-1734
Number of pages32
JournalMetallomics
Volume9
Issue number12
DOIs
StatePublished - Dec 1 2017

Fingerprint

Organoselenium Compounds
Selenoproteins
Glutathione Peroxidase
Sulfhydryl Compounds
Antioxidants
Pharmacology
Thioredoxin-Disulfide Reductase
Synthetic Chemistry Techniques
Glutathione Reductase
Redox reactions
Selenium
Trace Elements
Glutathione
Molecular Structure
Trace elements
Macromolecules
Sulfur
Chemical properties
Functional groups
Molecular structure

ASJC Scopus subject areas

  • Chemistry (miscellaneous)
  • Biophysics
  • Biomaterials
  • Biochemistry
  • Metals and Alloys

Cite this

Barbosa, N. V., Nogueira, C. W., Nogara, P. A., De Bem, A. F., Aschner, M., & Rocha, J. B. T. (2017). Organoselenium compounds as mimics of selenoproteins and thiol modifier agents. Metallomics, 9(12), 1703-1734. https://doi.org/10.1039/c7mt00083a

Organoselenium compounds as mimics of selenoproteins and thiol modifier agents. / Barbosa, Nilda V.; Nogueira, Cristina W.; Nogara, Pablo A.; De Bem, Andreza F.; Aschner, Michael; Rocha, João B.T.

In: Metallomics, Vol. 9, No. 12, 01.12.2017, p. 1703-1734.

Research output: Contribution to journalReview article

Barbosa, NV, Nogueira, CW, Nogara, PA, De Bem, AF, Aschner, M & Rocha, JBT 2017, 'Organoselenium compounds as mimics of selenoproteins and thiol modifier agents', Metallomics, vol. 9, no. 12, pp. 1703-1734. https://doi.org/10.1039/c7mt00083a
Barbosa NV, Nogueira CW, Nogara PA, De Bem AF, Aschner M, Rocha JBT. Organoselenium compounds as mimics of selenoproteins and thiol modifier agents. Metallomics. 2017 Dec 1;9(12):1703-1734. https://doi.org/10.1039/c7mt00083a
Barbosa, Nilda V. ; Nogueira, Cristina W. ; Nogara, Pablo A. ; De Bem, Andreza F. ; Aschner, Michael ; Rocha, João B.T. / Organoselenium compounds as mimics of selenoproteins and thiol modifier agents. In: Metallomics. 2017 ; Vol. 9, No. 12. pp. 1703-1734.
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