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. 2020 Jul 24;25(15):3354.
doi: 10.3390/molecules25153354.

Phenylselanyl Group Incorporation for "Glutathione Peroxidase-Like" Activity Modulation

Magdalena Obieziurska-Fabisiak  1 , Agata J Pacuła  1 , Lucia Capoccia  2 , Joanna Drogosz-Stachowicz  3 , Anna Janecka  3 , Claudio Santi  2 , Jacek Ścianowski  1
Affiliations

Phenylselanyl Group Incorporation for "Glutathione Peroxidase-Like" Activity Modulation

Magdalena Obieziurska-Fabisiak et al. Molecules. .

Abstract

The ability of organoselenium molecules to mimic the activity of the antioxidant selenoenzyme glutathione peroxidase (GPx) allows for their use as antioxidant or prooxidant modulators in several diseases associated with the disruption of the cell redox homeostasis. Current drug design in the field is partially based on specific modifications of the known Se-therapeutics aimed at achieving more selective bioactivity towards particular drug targets, accompanied by low toxicity as the therapeutic window for organoselenium compounds tends to be very narrow. Herein, we present a new group of Se-based antioxidants, structurally derived from the well-known group of GPx mimics-benzisoselenazol-3(2H)-ones. A series of N-substituted unsymmetrical phenylselenides with an o-amido function has been obtained by a newly developed procedure: a copper-catalyzed nucleophilic substitution by a Se-reagent formed in situ from diphenyl diselenide and sodium borohydride. All derivatives were tested as antioxidants and anticancer agents towards breast (MCF-7) and leukemia (HL-60) cancer cell lines. The highest H2O2-scavenging potential was observed for N-(3-methylbutyl)-2-(phenylselanyl)benzamide. The best antiproliferative activity was found for (-)-N-(1S,2R,4R)-menthyl-2-(phenylselanyl)benzamide (HL-60) and ((-)-N-(1S,2R,3S,6R)-(2-caranyl))benzamide (MCF-7). The structure-activity correlations, including the differences in reactivity of the obtained phenyl selenides and corresponding benzisoselenazol-3(2H)-ones, were performed.

Keywords: anticancer activity; antioxidant activity; selenides.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Scheme 1
Scheme 1
Bioactive organoselenium compounds 1–3 that possess aromatic rings in their structure.
Scheme 2
Scheme 2
Possible structural modification of N-substituted benzisozelenazol-3(2H)-ones 4.
Scheme 3
Scheme 3
Synthesis of N-substituted phenylselenides 7b–23b.
Scheme 4
Scheme 4
Putative mechanism for the Cu-catalyzed introduction of phenylselenyl group.
Scheme 5
Scheme 5
Results of the antioxidant activity measurements.
Scheme 6
Scheme 6
Plausible mechanism for the H2O2 reduction by the Se-catalysts in the presence of thiols.
Scheme 7
Scheme 7
Repetitive carbon chain in the structure of bio-active derivatives 18b, 28, 33 and 35.
See this image and copyright information in PMC

References

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