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Carbohydrate-Based NK1R Antagonists with Broad-Spectrum Anticancer Activity
[Image: see text] NK1R antagonists, investigated for the treatment of several pathologies, have shown encouraging results in the treatment of several cancers. In the present study, we report on the synthesis of carbohydrate-based NK1R antagonists and their evaluation as anticancer agents against a w...
Autores principales: | , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
American Chemical
Society
2021
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8529873/ https://www.ncbi.nlm.nih.gov/pubmed/34236855 http://dx.doi.org/10.1021/acs.jmedchem.1c00793 |
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author | Recio, Rocío Lerena, Patricia Pozo, Esther Calderón-Montaño, José Manuel Burgos-Morón, Estefanía López-Lázaro, Miguel Valdivia, Victoria Pernia Leal, Manuel Mouillac, Bernard Organero, Juan Ángel Khiar, Noureddine Fernández, Inmaculada |
author_facet | Recio, Rocío Lerena, Patricia Pozo, Esther Calderón-Montaño, José Manuel Burgos-Morón, Estefanía López-Lázaro, Miguel Valdivia, Victoria Pernia Leal, Manuel Mouillac, Bernard Organero, Juan Ángel Khiar, Noureddine Fernández, Inmaculada |
author_sort | Recio, Rocío |
collection | PubMed |
description | [Image: see text] NK1R antagonists, investigated for the treatment of several pathologies, have shown encouraging results in the treatment of several cancers. In the present study, we report on the synthesis of carbohydrate-based NK1R antagonists and their evaluation as anticancer agents against a wide range of cancer cells. All of the prepared compounds, derived from either d-galactose or l-arabinose, have shown high affinity and NK1R antagonistic activity with a broad-spectrum anticancer activity and an important selectivity, comparable to Cisplatin. This strategy has allowed us to identify the galactosyl derivative 14α, as an interesting hit exhibiting significant NK1R antagonist effect (k(inact) 0.209 ± 0.103 μM) and high binding affinity for NK1R (IC(50) = 50.4 nM, K(i) = 22.4 nM by measuring the displacement of [(125)I] SP from NK1R). Interestingly, this galactosyl derivative has shown marked selective cytotoxic activity against 12 different types of cancer cell lines. |
format | Online Article Text |
id | pubmed-8529873 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | American Chemical
Society |
record_format | MEDLINE/PubMed |
spelling | pubmed-85298732021-10-22 Carbohydrate-Based NK1R Antagonists with Broad-Spectrum Anticancer Activity Recio, Rocío Lerena, Patricia Pozo, Esther Calderón-Montaño, José Manuel Burgos-Morón, Estefanía López-Lázaro, Miguel Valdivia, Victoria Pernia Leal, Manuel Mouillac, Bernard Organero, Juan Ángel Khiar, Noureddine Fernández, Inmaculada J Med Chem [Image: see text] NK1R antagonists, investigated for the treatment of several pathologies, have shown encouraging results in the treatment of several cancers. In the present study, we report on the synthesis of carbohydrate-based NK1R antagonists and their evaluation as anticancer agents against a wide range of cancer cells. All of the prepared compounds, derived from either d-galactose or l-arabinose, have shown high affinity and NK1R antagonistic activity with a broad-spectrum anticancer activity and an important selectivity, comparable to Cisplatin. This strategy has allowed us to identify the galactosyl derivative 14α, as an interesting hit exhibiting significant NK1R antagonist effect (k(inact) 0.209 ± 0.103 μM) and high binding affinity for NK1R (IC(50) = 50.4 nM, K(i) = 22.4 nM by measuring the displacement of [(125)I] SP from NK1R). Interestingly, this galactosyl derivative has shown marked selective cytotoxic activity against 12 different types of cancer cell lines. American Chemical Society 2021-07-08 2021-07-22 /pmc/articles/PMC8529873/ /pubmed/34236855 http://dx.doi.org/10.1021/acs.jmedchem.1c00793 Text en © 2021 American Chemical Society 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 | Recio, Rocío Lerena, Patricia Pozo, Esther Calderón-Montaño, José Manuel Burgos-Morón, Estefanía López-Lázaro, Miguel Valdivia, Victoria Pernia Leal, Manuel Mouillac, Bernard Organero, Juan Ángel Khiar, Noureddine Fernández, Inmaculada Carbohydrate-Based NK1R Antagonists with Broad-Spectrum Anticancer Activity |
title | Carbohydrate-Based NK1R Antagonists with Broad-Spectrum
Anticancer Activity |
title_full | Carbohydrate-Based NK1R Antagonists with Broad-Spectrum
Anticancer Activity |
title_fullStr | Carbohydrate-Based NK1R Antagonists with Broad-Spectrum
Anticancer Activity |
title_full_unstemmed | Carbohydrate-Based NK1R Antagonists with Broad-Spectrum
Anticancer Activity |
title_short | Carbohydrate-Based NK1R Antagonists with Broad-Spectrum
Anticancer Activity |
title_sort | carbohydrate-based nk1r antagonists with broad-spectrum
anticancer activity |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8529873/ https://www.ncbi.nlm.nih.gov/pubmed/34236855 http://dx.doi.org/10.1021/acs.jmedchem.1c00793 |
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