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

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 6 nM) than selegiline. In general, the amino d...

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Detalles Bibliográficos
Autores: Matos, Maria João Correia Pinto Carvalho de, Rodríguez Enríquez, Fernanda, Vilar, Santiago, Santana Penín, María Lourdes, Uriarte Villares, Eugenio, Hripcsak, George, Estrada, Martín, Rodríguez Franco, María Isabel, Viña Castelao, María Dolores
Tipo de recurso: artículo
Fecha de publicación:2015
País:España
Institución:Universidad de Santiago de Compostela (USC)
Repositorio:Minerva. Repositorio Institucional de la Universidad de Santiago de Compostela
Idioma:inglés
OAI Identifier:oai:minerva.usc.gal:10347/23489
Acceso en línea:http://hdl.handle.net/10347/23489
Access Level:acceso abierto
Descripción
Sumario: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 6 nM) 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