MAO inhibitory activity of bromo-2phenylbenzofurans: synthesis, in vitro study, and docking calculations

• Tipo: Artigo em Revista Científica Internacional
• Data: 2017

Autores

Delogu, GL (Autor) Outra; Pintus, F (Autor) Outra; Mayan, L (Autor) Outra; Matos, MJ (Autor) Outra; Vilar, S (Autor) Outra; Munin, J (Autor) Outra; Fontenla, JA (Autor) Outra; Hripcsak, G (Autor) Outra; Fernanda Borges (Autor) FCUP; Vina, D (Autor) Outra

Revista

Título: MedChemComm

Vol. 8

Páginas: 1788-1796

ISSN: 2040-2503

Editora: Royal Society of Chemistry

Indexação

ISI Web of Knowledge - 10 Citações

Scopus - 10 Citações

Outras Informações

ID Authenticus: P-00N-20Y

DOI: 10.1039/c7md00311k

Abstract (EN): Monoamine oxidase (MAO) is an enzyme responsible for metabolism of monoamine neurotransmitters which play an important role in brain development and function. This enzyme exists in two isoforms, and it has been demonstrated that MAO-B activity, but not MAO-A activity, increases with aging. MAO inhibitors show clinical value because besides the monoamine level regulation they reduce the formation of byproducts of the MAO catalytic cycle, which are toxic to the brain. A series of 2-phenylbenzofuran derivatives was designed, synthesized and evaluated against hMAO-A and hMAO-B enzymes. A bromine substituent was introduced in the 2-phenyl ring, whereas position 5 or 7 of the benzofuran moiety was substituted with a methyl group. Most of the tested compounds inhibited preferentially MAO-B in a reversible manner, with IC50 values in the low micro or nanomolar range. The 2-( 2'-bromophenyl)-5-methylbenzofuran ( 5) was the most active compound identified (IC50 = 0.20 mu M). In addition, none of the studied compounds showed cytotoxic activity against the human neuroblastoma cell line SH-SY5Y. Molecular docking simulations were used to explain the observed hMAO-B structure-activity relationship for this type of compounds.

Idioma: Inglês

Tipo (Avaliação Docente): Científica

Nº de páginas: 9