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

• Type: Article in International Scientific Journal
• Date: 2012

Authors

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

Journal

Title: ChemMedChem

Vol. 7

ISSN: 1860-7179

Publisher: Wiley-Blackwell

Indexing

ISI Web of Knowledge - 55 Citations

Scopus - 57 Citations

Scientific classification

FOS: Natural sciences > Chemical sciences

CORDIS: Physical sciences > Chemistry > Applied chemistry > Pharmaceutical chemistry

Other information

Authenticus ID: 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.

Language: English

Type (Professor's evaluation): Scientific