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Synthesis of Quinoline and Dihydroquinoline Embelin Derivatives as Cardioprotective Agents
[Image: see text] A set of new dihydroquinoline embelin derivatives was obtained from the reaction of the natural benzoquinone embelin (1) with anilines and aromatic aldehydes in the presence of AgOTf. The synthesis of these compounds involves the formation of a Knoevenagel adduct, followed by nucle...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
American Chemical Society and American Society of Pharmacognosy
2023
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9972480/ https://www.ncbi.nlm.nih.gov/pubmed/36749898 http://dx.doi.org/10.1021/acs.jnatprod.2c00924 |
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author | Martín-Acosta, Pedro Cuadrado, Irene González-Cofrade, Laura Pestano, Roberto Hortelano, Sonsoles de las Heras, Beatriz Estévez-Braun, Ana |
author_facet | Martín-Acosta, Pedro Cuadrado, Irene González-Cofrade, Laura Pestano, Roberto Hortelano, Sonsoles de las Heras, Beatriz Estévez-Braun, Ana |
author_sort | Martín-Acosta, Pedro |
collection | PubMed |
description | [Image: see text] A set of new dihydroquinoline embelin derivatives was obtained from the reaction of the natural benzoquinone embelin (1) with anilines and aromatic aldehydes in the presence of AgOTf. The synthesis of these compounds involves the formation of a Knoevenagel adduct, followed by nucleophilic addition of aniline and subsequent electrocyclic ring closure. The scope of the reaction regarding the aldehydes and anilines was determined. Quinoline derivatives were also obtained from the corresponding dihydroquinolines under oxidation with DDQ. The cardioprotective activity of the synthesized compounds was screened using a doxorubicin-induced cardiotoxicity model in H9c2 cardiomyocytes. Some structure–activity relationships were outlined, and the best activities were achieved with quinoline-embelin derivatives having a 4-nitrophenyl group attached at the pyridine ring. The obtained results indicated that embelin derivatives 4i, 6a, 6d, 6k, and 6m could have potential as cardioprotective agents, as they attenuated a DOX-induced cardiotoxicity effect acting on oxidative stress and apoptosis. |
format | Online Article Text |
id | pubmed-9972480 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | American Chemical Society and American Society of Pharmacognosy |
record_format | MEDLINE/PubMed |
spelling | pubmed-99724802023-03-01 Synthesis of Quinoline and Dihydroquinoline Embelin Derivatives as Cardioprotective Agents Martín-Acosta, Pedro Cuadrado, Irene González-Cofrade, Laura Pestano, Roberto Hortelano, Sonsoles de las Heras, Beatriz Estévez-Braun, Ana J Nat Prod [Image: see text] A set of new dihydroquinoline embelin derivatives was obtained from the reaction of the natural benzoquinone embelin (1) with anilines and aromatic aldehydes in the presence of AgOTf. The synthesis of these compounds involves the formation of a Knoevenagel adduct, followed by nucleophilic addition of aniline and subsequent electrocyclic ring closure. The scope of the reaction regarding the aldehydes and anilines was determined. Quinoline derivatives were also obtained from the corresponding dihydroquinolines under oxidation with DDQ. The cardioprotective activity of the synthesized compounds was screened using a doxorubicin-induced cardiotoxicity model in H9c2 cardiomyocytes. Some structure–activity relationships were outlined, and the best activities were achieved with quinoline-embelin derivatives having a 4-nitrophenyl group attached at the pyridine ring. The obtained results indicated that embelin derivatives 4i, 6a, 6d, 6k, and 6m could have potential as cardioprotective agents, as they attenuated a DOX-induced cardiotoxicity effect acting on oxidative stress and apoptosis. American Chemical Society and American Society of Pharmacognosy 2023-02-07 /pmc/articles/PMC9972480/ /pubmed/36749898 http://dx.doi.org/10.1021/acs.jnatprod.2c00924 Text en © 2023 The Authors. Published by American Chemical Society and American Society of Pharmacognosy https://creativecommons.org/licenses/by/4.0/Permits the broadest form of re-use including for commercial purposes, provided that author attribution and integrity are maintained (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Martín-Acosta, Pedro Cuadrado, Irene González-Cofrade, Laura Pestano, Roberto Hortelano, Sonsoles de las Heras, Beatriz Estévez-Braun, Ana Synthesis of Quinoline and Dihydroquinoline Embelin Derivatives as Cardioprotective Agents |
title | Synthesis of
Quinoline and Dihydroquinoline Embelin
Derivatives as Cardioprotective Agents |
title_full | Synthesis of
Quinoline and Dihydroquinoline Embelin
Derivatives as Cardioprotective Agents |
title_fullStr | Synthesis of
Quinoline and Dihydroquinoline Embelin
Derivatives as Cardioprotective Agents |
title_full_unstemmed | Synthesis of
Quinoline and Dihydroquinoline Embelin
Derivatives as Cardioprotective Agents |
title_short | Synthesis of
Quinoline and Dihydroquinoline Embelin
Derivatives as Cardioprotective Agents |
title_sort | synthesis of
quinoline and dihydroquinoline embelin
derivatives as cardioprotective agents |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9972480/ https://www.ncbi.nlm.nih.gov/pubmed/36749898 http://dx.doi.org/10.1021/acs.jnatprod.2c00924 |
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