Article
Carbohydrate-Based NK1R Antagonists with Broad-Spectrum Anticancer Activity
Author/s | 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 |
Department | Universidad de Sevilla. Departamento de Química Orgánica y Farmacéutica Universidad de Sevilla. Departamento de Farmacología |
Publication Date | 2021 |
Deposit Date | 2021-11-26 |
Published in |
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Awards | Premio Anual Publicación Científica Destacada de la US. Facultad de Farmacia |
Abstract | 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 ... 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. |
Funding agencies | Consejo Superior de Investigaciones Científicas (CSIC) CSIC-COV19-047 |
Project ID. | 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 |
Citation | Recio Jiménez, R., Lerena Pérez, P., Pozo Torres, E., Calderón Montaño, J.M., Burgos Morón, E., López Lázaro, M.,...,Fernández Fernández, I. (2021). Carbohydrate-Based NK1R Antagonists with Broad-Spectrum Anticancer Activity. Journal of Medicinal Chemistry, 64 (14), 10350-10370. https://doi.org/10.1021/acs.jmedchem.1c00793. |
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