Synthesis and in vitro study of nitro- and methoxy-2-phenylbenzofurans as human Monoamine Oxidase inhibitors

A new series of 2-phenylbenzofuran derivatives were designed and synthesized to determine relevant structural features for the MAO inhibitory activity and selectivity. Methoxy substituents were introduced in the 2-phenyl ring, whereas the benzofuran moiety was not substituted or substituted at the p...

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Detalles Bibliográficos
Autores: Delogu, Giovanna Lucia, Kumar, Amit, Gatto, Gianluca, Bustelo Paz, Fernando, Saavedra, Lucía M, Rodríguez Franco, María Isabel, Laguna-Francia, Reyes, Viña Castelao, María Dolores
Tipo de recurso: artículo
Fecha de publicación:2021
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:10347/32623
Acceso en línea:http://hdl.handle.net/10347/32623
Access Level:acceso abierto
Palabra clave:3209
Descripción
Sumario:A new series of 2-phenylbenzofuran derivatives were designed and synthesized to determine relevant structural features for the MAO inhibitory activity and selectivity. Methoxy substituents were introduced in the 2-phenyl ring, whereas the benzofuran moiety was not substituted or substituted at the positions 5 or 7 with a nitro group. Substitution patterns on both the phenyl ring and the benzofuran moiety determine the affinity for MAO-A or MAO-B. The 2-(3-methoxyphenyl)-5-nitrobenzofuran 9 was the most potent MAO-B inhibitor (IC50 = 0.024 μM) identified in this series, whereas 7-nitro-2-phenylbenzofuran 7 was the most potent MAO-A inhibitor (IC50 = 0.168 μM), both acting as reversible inhibitors. The number and position of the methoxyl groups on the 2-phenyl ring, have an important influence on the inhibitory activity. Molecular docking studies confirmed the experimental results and highlighted the importance of key residues in enzyme inhibition.