Attachment of Chiral Functional Groups to Modify the Activity of New GPx Mimetics
A series of new chiral benzisoselenazol-3(2<i>H</i>)-ones and their corresponding diselenides bearing an <i>o</i>-amido function substituted on the nitrogen atom with various aliphatic and aromatic moieties were synthesized. All derivatives representing pairs of enantiomers o...
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2022-03-01
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| author | Anna Laskowska Agata Joanna Pacuła-Miszewska Angelika Długosz-Pokorska Anna Janecka Andrzej Wojtczak Jacek Ścianowski |
| author_facet | Anna Laskowska Agata Joanna Pacuła-Miszewska Angelika Długosz-Pokorska Anna Janecka Andrzej Wojtczak Jacek Ścianowski |
| author_sort | Anna Laskowska |
| collection | DOAJ |
| description | A series of new chiral benzisoselenazol-3(2<i>H</i>)-ones and their corresponding diselenides bearing an <i>o</i>-amido function substituted on the nitrogen atom with various aliphatic and aromatic moieties were synthesized. All derivatives representing pairs of enantiomers or diastereoisomers were obtained to thoroughly evaluate the three-dimensional structure–activity correlation. First, bensisoselenazol-3(2<i>H</i>)-ones were synthesized by reacting 2-(chloroseleno)benzoyl chloride with an appropriate enantiomerically pure amine. Then, the Se–N bond was cleaved by a reduction–oxidation procedure using sodium borohydride and then air oxidation to obtain the corresponding diselenides. All derivatives were tested as antioxidants and anticancer agents. In general, the diselenides were more reactive peroxide scavengers, with the highest activity observed for 2,2′-diselenobis[<i>N</i>-(1<i>S</i>,2<i>S</i>)-(-)-<i>trans</i>-2-hydroksy-1-indanylbezamide]. The most cytotoxic derivative towards human promyelocytic leukemia HL-60 and breast cancer MCF-7 cell lines was <i>N</i>-[(1<i>S</i>,2<i>R</i>)-(-)-<i>cis</i>-2-hydroksy-1-indanyl]-1,2-benzizoselenazol-3(2<i>H</i>)-one. The structure–activity relationship of the obtained organoselenium derivatives was discussed. |
| first_indexed | 2024-03-09T13:30:22Z |
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| id | doaj.art-a4c5202b186a4e1a91b67de65e5815c7 |
| institution | Directory Open Access Journal |
| issn | 1996-1944 |
| language | English |
| last_indexed | 2024-03-09T13:30:22Z |
| publishDate | 2022-03-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Materials |
| spelling | doaj.art-a4c5202b186a4e1a91b67de65e5815c72023-11-30T21:19:09ZengMDPI AGMaterials1996-19442022-03-01156206810.3390/ma15062068Attachment of Chiral Functional Groups to Modify the Activity of New GPx MimeticsAnna Laskowska0Agata Joanna Pacuła-Miszewska1Angelika Długosz-Pokorska2Anna Janecka3Andrzej Wojtczak4Jacek Ścianowski5Department 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, PolandDepartment 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, PolandDepartment of Crystallochemistry and Biocrystallography, Faculty of Chemistry, Nicolaus Copernicus University in Torun, 7 Gagarin Street, 87-100 Torun, PolandDepartment of Organic Chemistry, Faculty of Chemistry, Nicolaus Copernicus University, 7 Gagarin Street, 87-100 Torun, PolandA series of new chiral benzisoselenazol-3(2<i>H</i>)-ones and their corresponding diselenides bearing an <i>o</i>-amido function substituted on the nitrogen atom with various aliphatic and aromatic moieties were synthesized. All derivatives representing pairs of enantiomers or diastereoisomers were obtained to thoroughly evaluate the three-dimensional structure–activity correlation. First, bensisoselenazol-3(2<i>H</i>)-ones were synthesized by reacting 2-(chloroseleno)benzoyl chloride with an appropriate enantiomerically pure amine. Then, the Se–N bond was cleaved by a reduction–oxidation procedure using sodium borohydride and then air oxidation to obtain the corresponding diselenides. All derivatives were tested as antioxidants and anticancer agents. In general, the diselenides were more reactive peroxide scavengers, with the highest activity observed for 2,2′-diselenobis[<i>N</i>-(1<i>S</i>,2<i>S</i>)-(-)-<i>trans</i>-2-hydroksy-1-indanylbezamide]. The most cytotoxic derivative towards human promyelocytic leukemia HL-60 and breast cancer MCF-7 cell lines was <i>N</i>-[(1<i>S</i>,2<i>R</i>)-(-)-<i>cis</i>-2-hydroksy-1-indanyl]-1,2-benzizoselenazol-3(2<i>H</i>)-one. The structure–activity relationship of the obtained organoselenium derivatives was discussed.https://www.mdpi.com/1996-1944/15/6/2068benzisoselenazol-3(2<i>H</i>)-onesdiselenidespharmacophoreantioxidant activityantiproliferative activity |
| spellingShingle | Anna Laskowska Agata Joanna Pacuła-Miszewska Angelika Długosz-Pokorska Anna Janecka Andrzej Wojtczak Jacek Ścianowski Attachment of Chiral Functional Groups to Modify the Activity of New GPx Mimetics Materials benzisoselenazol-3(2<i>H</i>)-ones diselenides pharmacophore antioxidant activity antiproliferative activity |
| title | Attachment of Chiral Functional Groups to Modify the Activity of New GPx Mimetics |
| title_full | Attachment of Chiral Functional Groups to Modify the Activity of New GPx Mimetics |
| title_fullStr | Attachment of Chiral Functional Groups to Modify the Activity of New GPx Mimetics |
| title_full_unstemmed | Attachment of Chiral Functional Groups to Modify the Activity of New GPx Mimetics |
| title_short | Attachment of Chiral Functional Groups to Modify the Activity of New GPx Mimetics |
| title_sort | attachment of chiral functional groups to modify the activity of new gpx mimetics |
| topic | benzisoselenazol-3(2<i>H</i>)-ones diselenides pharmacophore antioxidant activity antiproliferative activity |
| url | https://www.mdpi.com/1996-1944/15/6/2068 |
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