2. Academic Validation
  3. Carbohydrate-Based NK1R Antagonists with Broad-Spectrum Anticancer Activity

Carbohydrate-Based NK1R Antagonists with Broad-Spectrum Anticancer Activity

  • J Med Chem. 2021 Jul 22;64(14):10350-10370. doi: 10.1021/acs.jmedchem.1c00793.
Rocío Recio 1,  Patricia Lerena 1,  Esther Pozo 1,  José Manuel Calderón-Montaño 2,  Estefanía Burgos-Morón 2,  Miguel López-Lázaro 2,  Victoria Valdivia 1,  Manuel Pernia Leal 1,  Bernard Mouillac 3,  Juan Ángel Organero 4,  Noureddine Khiar 5,  Inmaculada Fernández 1
Affiliations

Affiliations

  • 1 Departamento de Química Orgánica y Farmacéutica, Facultad de Farmacia, Universidad de Sevilla, C/ Profesor García González, 2, 41012 Sevilla, Spain.
  • 2 Departamento de Farmacología, Facultad de Farmacia, Universidad de Sevilla, C/ Profesor García González, 2, 41012 Sevilla, Spain.
  • 3 Institut de Génomique Fonctionnelle (IGF), INSERM, Université de Montpellier, CNRS, F-34094 Montpellier, France.
  • 4 Departamento de Química Física, Facultad de Ciencias Ambientales y Bioquímicas and INAMOL, Universidad de Castilla-La Mancha, Avenida Carlos III, s/n, 45071 Toledo, Spain.
  • 5 Instituto de Investigaciones Químicas (IIQ), CSIC-Universidad de Sevilla, Avenida Américo Vespucio, 49, Isla de la Cartuja, 41092 Sevilla, Spain.
PMID: 34236855 DOI: 10.1021/acs.jmedchem.1c00793
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 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 (kinact 0.209 ± 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.

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