8-Substituted 3-Arylcoumarins as Potent and Selective MAO-B Inhibitors: Synthesis, Pharmacological Evaluation, and Docking Studies

• Tipo: Artigo em Revista Científica Internacional
• Data: 2012

Autores

Dolores Vina (Autor) Outra; Matos, MJ (Autor) Outra; Giulio Ferino (Autor) Outra; Enzo Cadoni (Autor) Outra; Reyes Laguna (Autor) Outra; Fernanda Borges (Autor) FCUP; Eugenio Uriarte (Autor) Outra; Lourdes Santana (Autor) Outra

Revista

Título: ChemMedChem

Vol. 7

ISSN: 1860-7179

Editora: Wiley-Blackwell

Indexação

ISI Web of Knowledge - 55 Citações

Scopus - 57 Citações

Classificação Científica

FOS: Ciências exactas e naturais > Química

CORDIS: Ciências Físicas > Química > Química aplicada > Química farmacêutica

Outras Informações

ID Authenticus: P-002-C5C

Abstract (EN): Neurodegenerative disorders are becoming more prevalent given the increase in the aging population. This has inspired active research in the development of new drugs that could mark an important advance in the treatment of complex diseases such as Alzheimer's and Parkinson's. With the aim of finding new MAO-B-selective inhibitors, we report the synthesis, in vitro evaluation, and docking simulation of a new series of 3-arylcoumarins variously substituted at the 8-position. Most of the studied compounds show high affinity and selectivity for the hMAO-B isoform, with IC50 values in the low micro- to nanomolar range. Some of them have greater hMAO-B inhibitory activity and selectivity than the reference compound, selegiline. Compounds 7 and 8 are the most active of this series, with compound 8 being fivefold more potent against MAO-B and severalfold more selective than selegiline. Docking experiments were carried out with hMAO-B crystal structures, providing new information about the enzymeinhibitor interaction and the potential therapeutic application of the new 8-substituted 3-arylcoumarins.

Idioma: Inglês

Tipo (Avaliação Docente): Científica