Phenylselanyl Group Incorporation for “Glutathione Peroxidase-Like” Activity Modulation
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 i...
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MDPI AG
2020-07-01
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| Series: | Molecules |
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| Online Access: | https://www.mdpi.com/1420-3049/25/15/3354 |
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| author | Magdalena Obieziurska-Fabisiak Agata J. Pacuła Lucia Capoccia Joanna Drogosz-Stachowicz Anna Janecka Claudio Santi Jacek Ścianowski |
| author_facet | Magdalena Obieziurska-Fabisiak Agata J. Pacuła Lucia Capoccia Joanna Drogosz-Stachowicz Anna Janecka Claudio Santi Jacek Ścianowski |
| author_sort | Magdalena Obieziurska-Fabisiak |
| collection | DOAJ |
| description | 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(2<i>H</i>)-ones. A series of <i>N</i>-substituted unsymmetrical phenylselenides with an <i>o</i>-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 H<sub>2</sub>O<sub>2</sub>-scavenging potential was observed for <i>N</i>-(3-methylbutyl)-2-(phenylselanyl)benzamide. The best antiproliferative activity was found for (−)-<i>N</i>-(1<i>S</i>,2<i>R</i>,4<i>R</i>)-menthyl-2-(phenylselanyl)benzamide (HL-60) and ((−)-<i>N-(1S,2R,3S,6R</i>)-(2-caranyl))benzamide (MCF-7). The structure–activity correlations, including the differences in reactivity of the obtained phenyl selenides and corresponding benzisoselenazol-3(2<i>H</i>)-ones, were performed. |
| first_indexed | 2024-03-10T18:14:36Z |
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| id | doaj.art-05cae97af5d44f30b8894ada185d1186 |
| institution | Directory Open Access Journal |
| issn | 1420-3049 |
| language | English |
| last_indexed | 2024-03-10T18:14:36Z |
| publishDate | 2020-07-01 |
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| series | Molecules |
| spelling | doaj.art-05cae97af5d44f30b8894ada185d11862023-11-20T07:47:19ZengMDPI AGMolecules1420-30492020-07-012515335410.3390/molecules25153354Phenylselanyl Group Incorporation for “Glutathione Peroxidase-Like” Activity ModulationMagdalena Obieziurska-Fabisiak0Agata J. Pacuła1Lucia Capoccia2Joanna Drogosz-Stachowicz3Anna Janecka4Claudio Santi5Jacek Ścianowski6Department of Organic Chemistry, Faculty of Chemistry, Nicolaus Copernicus University, 7 Gagarin Street, 87-100 Torun, PolandDepartment of Organic Chemistry, Faculty of Chemistry, Nicolaus Copernicus University, 7 Gagarin Street, 87-100 Torun, PolandDipartimento di Scienze Farmaceutiche, Universita di Perugia, Via del Liceo 1, 06134 Perugia, ItalyDepartment of Biomolecular Chemistry, Faculty of Medicine, Medical University of Lodz, Mazowiecka 6/8, 92-215 Lodz, PolandDepartment of Biomolecular Chemistry, Faculty of Medicine, Medical University of Lodz, Mazowiecka 6/8, 92-215 Lodz, PolandDipartimento di Scienze Farmaceutiche, Universita di Perugia, Via del Liceo 1, 06134 Perugia, ItalyDepartment of Organic Chemistry, Faculty of Chemistry, Nicolaus Copernicus University, 7 Gagarin Street, 87-100 Torun, PolandThe 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(2<i>H</i>)-ones. A series of <i>N</i>-substituted unsymmetrical phenylselenides with an <i>o</i>-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 H<sub>2</sub>O<sub>2</sub>-scavenging potential was observed for <i>N</i>-(3-methylbutyl)-2-(phenylselanyl)benzamide. The best antiproliferative activity was found for (−)-<i>N</i>-(1<i>S</i>,2<i>R</i>,4<i>R</i>)-menthyl-2-(phenylselanyl)benzamide (HL-60) and ((−)-<i>N-(1S,2R,3S,6R</i>)-(2-caranyl))benzamide (MCF-7). The structure–activity correlations, including the differences in reactivity of the obtained phenyl selenides and corresponding benzisoselenazol-3(2<i>H</i>)-ones, were performed.https://www.mdpi.com/1420-3049/25/15/3354selenidesantioxidant activityanticancer activity |
| spellingShingle | Magdalena Obieziurska-Fabisiak Agata J. Pacuła Lucia Capoccia Joanna Drogosz-Stachowicz Anna Janecka Claudio Santi Jacek Ścianowski Phenylselanyl Group Incorporation for “Glutathione Peroxidase-Like” Activity Modulation Molecules selenides antioxidant activity anticancer activity |
| title | Phenylselanyl Group Incorporation for “Glutathione Peroxidase-Like” Activity Modulation |
| title_full | Phenylselanyl Group Incorporation for “Glutathione Peroxidase-Like” Activity Modulation |
| title_fullStr | Phenylselanyl Group Incorporation for “Glutathione Peroxidase-Like” Activity Modulation |
| title_full_unstemmed | Phenylselanyl Group Incorporation for “Glutathione Peroxidase-Like” Activity Modulation |
| title_short | Phenylselanyl Group Incorporation for “Glutathione Peroxidase-Like” Activity Modulation |
| title_sort | phenylselanyl group incorporation for glutathione peroxidase like activity modulation |
| topic | selenides antioxidant activity anticancer activity |
| url | https://www.mdpi.com/1420-3049/25/15/3354 |
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