title: Potent and selective MAO-B inhibitory activity: amino- versus nitro-3-arylcoumarin derivatives.
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.
authors.affiliation: Departamento de Química Orgánica, Facultad de Farmacia, Universidad de Santiago de Compostela, 15782 Santiago de Compostela, Spain. Electronic address: mariacmatos@gmail.com.
authors.forename: Maria João
authors.initials: MJ
authors.lastname: Matos
authors.affiliation: Departamento de Farmacología, CIMUS, Universidad de Santiago de Compostela, 15782 Santiago de Compostela, Spain.
authors.forename: Fernanda
authors.initials: F
authors.lastname: Rodríguez-Enríquez
authors.affiliation: 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.
authors.forename: Santiago
authors.initials: S
authors.lastname: Vilar
authors.affiliation: Departamento de Química Orgánica, Facultad de Farmacia, Universidad de Santiago de Compostela, 15782 Santiago de Compostela, Spain.
authors.forename: Lourdes
authors.initials: L
authors.lastname: Santana
authors.affiliation: Departamento de Química Orgánica, Facultad de Farmacia, Universidad de Santiago de Compostela, 15782 Santiago de Compostela, Spain.
authors.forename: Eugenio
authors.initials: E
authors.lastname: Uriarte
authors.affiliation: Department of Biomedical Informatics, Columbia University Medical Center, 10032 New York, USA.
authors.forename: George
authors.initials: G
authors.lastname: Hripcsak
authors.affiliation: Instituto de Química Médica, Consejo Superior de Investigaciones Científicas (IQM-CSIC), C/Juan de la Cierva 3, 28006 Madrid, Spain.
authors.forename: Martín
authors.initials: M
authors.lastname: Estrada
authors.affiliation: Instituto de Química Médica, Consejo Superior de Investigaciones Científicas (IQM-CSIC), C/Juan de la Cierva 3, 28006 Madrid, Spain.
authors.forename: María Isabel
authors.initials: MI
authors.lastname: Rodríguez-Franco
authors.affiliation: Departamento de Farmacología, CIMUS, Universidad de Santiago de Compostela, 15782 Santiago de Compostela, Spain.
authors.forename: Dolores
authors.initials: D
authors.lastname: Viña
mesh_terms: D001665:Binding Sites; D003374:Coumarins / Q000737:chemistry* / Q000378:metabolism; D006801:Humans; D062105:Molecular Docking Simulation; D008995:Monoamine Oxidase / Q000737:chemistry* / Q000378:metabolism; D008996:Monoamine Oxidase Inhibitors / Q000737:chemistry* / Q000378:metabolism; D011485:Protein Binding; D020033:Protein Isoforms / Q000037:antagonists & inhibitors / Q000378:metabolism; D017434:Protein Structure, Tertiary; D012642:Selegiline / Q000737:chemistry / Q000378:metabolism; D013329:Structure-Activity Relationship
chemical_list: D003374:Coumarins; D008996:Monoamine Oxidase Inhibitors; D020033:Protein Isoforms; D012642:Selegiline; D008995:Monoamine Oxidase
keywords: 3-Arylcoumarins; ADME theoretical properties; Docking studies; Monoamine oxidase inhibitors; PAMPA assay; Perkin reaction