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Synthesis and Vasorelaxant Activity of Nitrate−Coumarin Derivatives
Due to the need for new chemical entities for cardiovascular diseases, we have synthesized a new series of nitrate−coumarins and evaluated their vasorelaxant activity in contraction‐relaxation studies using rat aorta rings precontracted with phenylephrine or by depolarization with a high concentrati...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
John Wiley and Sons Inc.
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9827831/ https://www.ncbi.nlm.nih.gov/pubmed/36109344 http://dx.doi.org/10.1002/cmdc.202200476 |
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author | Matos, Maria João Uriarte, Eugenio Seoane, Nuria Picos, Aitor Gil‐Longo, José Campos‐Toimil, Manuel |
author_facet | Matos, Maria João Uriarte, Eugenio Seoane, Nuria Picos, Aitor Gil‐Longo, José Campos‐Toimil, Manuel |
author_sort | Matos, Maria João |
collection | PubMed |
description | Due to the need for new chemical entities for cardiovascular diseases, we have synthesized a new series of nitrate−coumarins and evaluated their vasorelaxant activity in contraction‐relaxation studies using rat aorta rings precontracted with phenylephrine or by depolarization with a high concentration of potassium chloride. Four of the new compounds were able to relax smooth vascular muscle with a similar profile and potency to glyceryl trinitrate (IC(50)=12.73 nM) and sodium nitroprusside (IC(50)=4.32 nM). Coumarin‐7‐yl‐methyl nitrate (4), the best compound within the series, was able to relax smooth vascular muscle in the low nanomolar range (IC(50)=1.92 nM). The mechanisms of action have been explored, being the activation of sGC and the opening of K(+) channels involved. Our studies indicate that the new nitrate derivatives are reversible and not deleterious for aortic rings, suggesting that these compounds have a potential interest for the development of new and highly efficient vasodilator drugs. |
format | Online Article Text |
id | pubmed-9827831 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | John Wiley and Sons Inc. |
record_format | MEDLINE/PubMed |
spelling | pubmed-98278312023-01-10 Synthesis and Vasorelaxant Activity of Nitrate−Coumarin Derivatives Matos, Maria João Uriarte, Eugenio Seoane, Nuria Picos, Aitor Gil‐Longo, José Campos‐Toimil, Manuel ChemMedChem Research Articles Due to the need for new chemical entities for cardiovascular diseases, we have synthesized a new series of nitrate−coumarins and evaluated their vasorelaxant activity in contraction‐relaxation studies using rat aorta rings precontracted with phenylephrine or by depolarization with a high concentration of potassium chloride. Four of the new compounds were able to relax smooth vascular muscle with a similar profile and potency to glyceryl trinitrate (IC(50)=12.73 nM) and sodium nitroprusside (IC(50)=4.32 nM). Coumarin‐7‐yl‐methyl nitrate (4), the best compound within the series, was able to relax smooth vascular muscle in the low nanomolar range (IC(50)=1.92 nM). The mechanisms of action have been explored, being the activation of sGC and the opening of K(+) channels involved. Our studies indicate that the new nitrate derivatives are reversible and not deleterious for aortic rings, suggesting that these compounds have a potential interest for the development of new and highly efficient vasodilator drugs. John Wiley and Sons Inc. 2022-10-13 2022-11-04 /pmc/articles/PMC9827831/ /pubmed/36109344 http://dx.doi.org/10.1002/cmdc.202200476 Text en © 2022 The Authors. ChemMedChem published by Wiley-VCH GmbH https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc-nd/4.0/ (https://creativecommons.org/licenses/by-nc-nd/4.0/) License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made. |
spellingShingle | Research Articles Matos, Maria João Uriarte, Eugenio Seoane, Nuria Picos, Aitor Gil‐Longo, José Campos‐Toimil, Manuel Synthesis and Vasorelaxant Activity of Nitrate−Coumarin Derivatives |
title | Synthesis and Vasorelaxant Activity of Nitrate−Coumarin Derivatives |
title_full | Synthesis and Vasorelaxant Activity of Nitrate−Coumarin Derivatives |
title_fullStr | Synthesis and Vasorelaxant Activity of Nitrate−Coumarin Derivatives |
title_full_unstemmed | Synthesis and Vasorelaxant Activity of Nitrate−Coumarin Derivatives |
title_short | Synthesis and Vasorelaxant Activity of Nitrate−Coumarin Derivatives |
title_sort | synthesis and vasorelaxant activity of nitrate−coumarin derivatives |
topic | Research Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9827831/ https://www.ncbi.nlm.nih.gov/pubmed/36109344 http://dx.doi.org/10.1002/cmdc.202200476 |
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