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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...

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Autores principales: 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
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Chemical Society 2021
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.
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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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