MAO Inhibitory Activity of 2-Arylbenzofurans versus 3-Arylcoumarins: Synthesis, invitro Study, and Docking Calculations

• Tipo: Artigo em Revista Científica Internacional
• Data: 2013

Autores

Ferino, G (Autor) Outra; Cadoni, E (Autor) Outra; Matos, MJ (Autor) Outra; Elias Quezada (Autor) FCUP; Uriarte, E (Autor) Outra; Santana, L (Autor) Outra; Vilar, S (Autor) Outra; Tatonetti, NP (Autor) Outra; Yanez, M (Autor) Outra; Vina, D (Autor) Outra; Picciau, C (Autor) Outra; Serra, S (Autor) Outra; Delogu, G (Autor) Outra

Revista

Título: ChemMedChem

Vol. 8

Páginas: 956-966

ISSN: 1860-7179

Editora: Wiley-Blackwell

Indexação

Scopus - 26 Citações

Outras Informações

ID Authenticus: P-008-B72

DOI: 10.1002/cmdc.201300048

Abstract (EN): Monoamine oxidase (MAO) is an important drug target for the treatment of neurological disorders. Several 3-arylcoumarin derivatives were previously described as interesting selective MAO-B inhibitors. Preserving the trans-stilbene structure, a series of 2-arylbenzofuran and corresponding 3-arylcoumarin derivatives were synthesized and evaluated as inhibitors of both MAO isoforms, MAO-A and MAO-B. In general, both types of derivatives were found to be selective MAO-B inhibitors, with IC50 values in the nano- to micromolar range. 5-Nitro-2-(4-methoxyphenyl)benzofuran (8) is the most active compound of the benzofuran series, presenting MAO-B selectivity and reversible inhibition (IC50=140nM). 3-(4¿-Methoxyphenyl)-6-nitrocoumarin (15), with the same substitution pattern as that of compound 8, was found to be the most active MAO-B inhibitor of the coumarin series (IC50=3nM). However, 3-phenylcoumarin 14 showed activity in the same range (IC50=6nM), is reversible, and also severalfold more selective than compound 15. Docking experiments for the most active compounds into the MAO-B and MAO-A binding pockets highlighted different interactions between the derivative classes (2-arylbenzofurans and 3-arylcoumarins), and provided new information about the enzyme-inhibitor interaction and the potential therapeutic application of these scaffolds. © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Idioma: Inglês

Tipo (Avaliação Docente): Científica