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Attachment of Chiral Functional Groups to Modify the Activity of New GPx Mimetics

A series of new chiral benzisoselenazol-3(2H)-ones and their corresponding diselenides bearing an o-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 th...

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Autores principales: Laskowska, Anna, Pacuła-Miszewska, Agata Joanna, Długosz-Pokorska, Angelika, Janecka, Anna, Wojtczak, Andrzej, Ścianowski, Jacek
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8950439/
https://www.ncbi.nlm.nih.gov/pubmed/35329523
http://dx.doi.org/10.3390/ma15062068
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author Laskowska, Anna
Pacuła-Miszewska, Agata Joanna
Długosz-Pokorska, Angelika
Janecka, Anna
Wojtczak, Andrzej
Ścianowski, Jacek
author_facet Laskowska, Anna
Pacuła-Miszewska, Agata Joanna
Długosz-Pokorska, Angelika
Janecka, Anna
Wojtczak, Andrzej
Ścianowski, Jacek
author_sort Laskowska, Anna
collection PubMed
description A series of new chiral benzisoselenazol-3(2H)-ones and their corresponding diselenides bearing an o-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(2H)-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[N-(1S,2S)-(-)-trans-2-hydroksy-1-indanylbezamide]. The most cytotoxic derivative towards human promyelocytic leukemia HL-60 and breast cancer MCF-7 cell lines was N-[(1S,2R)-(-)-cis-2-hydroksy-1-indanyl]-1,2-benzizoselenazol-3(2H)-one. The structure–activity relationship of the obtained organoselenium derivatives was discussed.
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spelling pubmed-89504392022-03-26 Attachment of Chiral Functional Groups to Modify the Activity of New GPx Mimetics Laskowska, Anna Pacuła-Miszewska, Agata Joanna Długosz-Pokorska, Angelika Janecka, Anna Wojtczak, Andrzej Ścianowski, Jacek Materials (Basel) Article A series of new chiral benzisoselenazol-3(2H)-ones and their corresponding diselenides bearing an o-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(2H)-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[N-(1S,2S)-(-)-trans-2-hydroksy-1-indanylbezamide]. The most cytotoxic derivative towards human promyelocytic leukemia HL-60 and breast cancer MCF-7 cell lines was N-[(1S,2R)-(-)-cis-2-hydroksy-1-indanyl]-1,2-benzizoselenazol-3(2H)-one. The structure–activity relationship of the obtained organoselenium derivatives was discussed. MDPI 2022-03-11 /pmc/articles/PMC8950439/ /pubmed/35329523 http://dx.doi.org/10.3390/ma15062068 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Laskowska, Anna
Pacuła-Miszewska, Agata Joanna
Długosz-Pokorska, Angelika
Janecka, Anna
Wojtczak, Andrzej
Ścianowski, Jacek
Attachment of Chiral Functional Groups to Modify the Activity of New GPx Mimetics
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 Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8950439/
https://www.ncbi.nlm.nih.gov/pubmed/35329523
http://dx.doi.org/10.3390/ma15062068
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