2. Academic Validation
  3. Potent and selective MAO-B inhibitory activity: amino- versus nitro-3-arylcoumarin derivatives

Potent and selective MAO-B inhibitory activity: amino- versus nitro-3-arylcoumarin derivatives

  • Bioorg Med Chem Lett. 2015 Feb 1;25(3):642-8. doi: 10.1016/j.bmcl.2014.12.001.
Maria João Matos 1,  Fernanda Rodríguez-Enríquez 2,  Santiago Vilar 3,  Lourdes Santana 4,  Eugenio Uriarte 4,  George Hripcsak 5,  Martín Estrada 6,  María Isabel Rodríguez-Franco 6,  Dolores Viña 2
Affiliations

Affiliations

  • 1 Departamento de Química Orgánica, Facultad de Farmacia, Universidad de Santiago de Compostela, 15782 Santiago de Compostela, Spain. Electronic address: mariacmatos@gmail.com.
  • 2 Departamento de Farmacología, CIMUS, Universidad de Santiago de Compostela, 15782 Santiago de Compostela, Spain.
  • 3 Departamento de Química Orgánica, Facultad de Farmacia, Universidad de Santiago de Compostela, 15782 Santiago de Compostela, Spain; Department of Biomedical Informatics, Columbia University Medical Center, 10032 New York, USA.
  • 4 Departamento de Química Orgánica, Facultad de Farmacia, Universidad de Santiago de Compostela, 15782 Santiago de Compostela, Spain.
  • 5 Department of Biomedical Informatics, Columbia University Medical Center, 10032 New York, USA.
  • 6 Instituto de Química Médica, Consejo Superior de Investigaciones Científicas (IQM-CSIC), C/Juan de la Cierva 3, 28006 Madrid, Spain.
PMID: 25532905 DOI: 10.1016/j.bmcl.2014.12.001
Abstract

In this study we synthesized and evaluated a new series of amino and nitro 3-arylcoumarins as hMAO-A and hMAO-B inhibitors. Compounds 2, 3, 5 and 6 presented a better activity and selectivity profile against the hMAO-B isoform (IC50 values between 2 and 6nM) than selegiline. In general, the amino derivatives (4-6) proved to be more selective against MAO-B than the nitro derivatives (1-3). Additionally, a theoretical study of some physicochemical properties, PAMPA and reversibility assays for the most potent derivative, and molecular docking simulations were carried out to further explain the pharmacological results, and to identify the hypothetical binding mode for the compounds inside the hMAO-B.

Keywords

3-Arylcoumarins; ADME theoretical properties; Docking studies; Monoamine oxidase inhibitors; PAMPA assay; Perkin reaction.

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