Carbohydrate-Based NK1R Antagonists with Broad-Spectrum Anticancer Activity

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 cance...

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Autores: Recio Jiménez, Rocío, Lerena Pérez, Patricia, Pozo Torres, Esther, Calderón Montaño, José Manuel, Burgos Morón, Estefanía, López Lázaro, Miguel, Valdivia Giménez, Victoria Esther, Pernia Leal, Manuel, Mouillac, Bernard, Organero, Juan Ángel, Khiar, Noureddine, Fernández Fernández, Inmaculada
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2021
País:España
Institución:Universidad de Sevilla (US)
Repositorio:idUS. Depósito de Investigación de la Universidad de Sevilla
OAI Identifier:oai:idus.us.es:11441/127707
Acceso en línea:https://hdl.handle.net/11441/127707
https://doi.org/10.1021/acs.jmedchem.1c00793
Access Level:acceso abierto
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spelling Carbohydrate-Based NK1R Antagonists with Broad-Spectrum Anticancer ActivityRecio Jiménez, RocíoLerena Pérez, PatriciaPozo Torres, EstherCalderón Montaño, José ManuelBurgos Morón, EstefaníaLópez Lázaro, MiguelValdivia Giménez, Victoria EstherPernia Leal, ManuelMouillac, BernardOrganero, Juan ÁngelKhiar, NoureddineFernández Fernández, InmaculadaNK1R 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-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 (kinact0.209 ± 0.103 μM) and high binding affinity for NK1R (IC50= 50.4 nM,Ki= 22.4 nM by measuring the displacement of [125I] SP from NK1R). Interestingly, this galactosyl derivative has shown marked selective cytotoxic activity against 12 different types of cancer cell lines.Ministerio de Economía y Competitividad CTQ2016-78580-C2- 2-R, CTQ2016-78580-C2-1-R, CTQ2017-86655-R, PID2019-104767RB-I00Ministerio de Ciencia e Innovación PID2019-104767RB-I00Junta de Andalucía P06-FQM-01852, CV20-04221, FQM-313, FQM-102Premio Anual Publicación Científica Destacada de la US. Facultad de FarmaciaAmerican Chemical SocietyQuímica Orgánica y FarmacéuticaFarmacologíaConsejo Superior de Investigaciones Científicas (CSIC) CSIC-COV19-0472021info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionapplication/pdfapplication/pdfhttps://hdl.handle.net/11441/127707https://doi.org/10.1021/acs.jmedchem.1c00793reponame:idUS. Depósito de Investigación de la Universidad de Sevillainstname:Universidad de Sevilla (US)InglésJournal of Medicinal Chemistry, 64 (14), 10350-10370.CTQ2016-78580-C2- 2-RCTQ2016-78580-C2-1-RCTQ2017-86655-RPID2019-104767RB-I00PID2019-104767RB-I00P06-FQM-01852CV20-04221FQM-313FQM-102CSIC-COV19-047https://doi.org/10.1021/acs.jmedchem.1c00793info:eu-repo/semantics/openAccessoai:idus.us.es:11441/1277072026-06-17T12:51:07Z
dc.title.none.fl_str_mv Carbohydrate-Based NK1R Antagonists with Broad-Spectrum Anticancer Activity
title Carbohydrate-Based NK1R Antagonists with Broad-Spectrum Anticancer Activity
spellingShingle Carbohydrate-Based NK1R Antagonists with Broad-Spectrum Anticancer Activity
Recio Jiménez, Rocío
title_short 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_sort Carbohydrate-Based NK1R Antagonists with Broad-Spectrum Anticancer Activity
dc.creator.none.fl_str_mv Recio Jiménez, Rocío
Lerena Pérez, Patricia
Pozo Torres, Esther
Calderón Montaño, José Manuel
Burgos Morón, Estefanía
López Lázaro, Miguel
Valdivia Giménez, Victoria Esther
Pernia Leal, Manuel
Mouillac, Bernard
Organero, Juan Ángel
Khiar, Noureddine
Fernández Fernández, Inmaculada
author Recio Jiménez, Rocío
author_facet Recio Jiménez, Rocío
Lerena Pérez, Patricia
Pozo Torres, Esther
Calderón Montaño, José Manuel
Burgos Morón, Estefanía
López Lázaro, Miguel
Valdivia Giménez, Victoria Esther
Pernia Leal, Manuel
Mouillac, Bernard
Organero, Juan Ángel
Khiar, Noureddine
Fernández Fernández, Inmaculada
author_role author
author2 Lerena Pérez, Patricia
Pozo Torres, Esther
Calderón Montaño, José Manuel
Burgos Morón, Estefanía
López Lázaro, Miguel
Valdivia Giménez, Victoria Esther
Pernia Leal, Manuel
Mouillac, Bernard
Organero, Juan Ángel
Khiar, Noureddine
Fernández Fernández, Inmaculada
author2_role author
author
author
author
author
author
author
author
author
author
author
dc.contributor.none.fl_str_mv Química Orgánica y Farmacéutica
Farmacología
Consejo Superior de Investigaciones Científicas (CSIC) CSIC-COV19-047
description 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-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 (kinact0.209 ± 0.103 μM) and high binding affinity for NK1R (IC50= 50.4 nM,Ki= 22.4 nM by measuring the displacement of [125I] SP from NK1R). Interestingly, this galactosyl derivative has shown marked selective cytotoxic activity against 12 different types of cancer cell lines.
publishDate 2021
dc.date.none.fl_str_mv 2021
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv https://hdl.handle.net/11441/127707
https://doi.org/10.1021/acs.jmedchem.1c00793
url https://hdl.handle.net/11441/127707
https://doi.org/10.1021/acs.jmedchem.1c00793
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv Journal of Medicinal Chemistry, 64 (14), 10350-10370.
CTQ2016-78580-C2- 2-R
CTQ2016-78580-C2-1-R
CTQ2017-86655-R
PID2019-104767RB-I00
PID2019-104767RB-I00
P06-FQM-01852
CV20-04221
FQM-313
FQM-102
CSIC-COV19-047
https://doi.org/10.1021/acs.jmedchem.1c00793
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
application/pdf
dc.publisher.none.fl_str_mv American Chemical Society
publisher.none.fl_str_mv American Chemical Society
dc.source.none.fl_str_mv reponame:idUS. Depósito de Investigación de la Universidad de Sevilla
instname:Universidad de Sevilla (US)
instname_str Universidad de Sevilla (US)
reponame_str idUS. Depósito de Investigación de la Universidad de Sevilla
collection idUS. Depósito de Investigación de la Universidad de Sevilla
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score 15.301603

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