2021-11-262021-11-262021Recio 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.1c00793.0022-26231520-4804https://hdl.handle.net/11441/127707NK1R 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.application/pdf21 p.engAttribution-NonCommercial-NoDerivatives 4.0 Internacionalhttp://creativecommons.org/licenses/by-nc-nd/4.0/info:eu-repo/semantics/articleinfo:eu-repo/semantics/openAccess10.1021/acs.jmedchem.1c00793