Potent and selective MAO-B inhibitory activity: Amino- versus nitro-3-arylcoumarin derivatives

• Type: Article in International Scientific Journal
• Date: 2015

Authors

Matos, MJ (Author) Other; Rodríguez Enríquez, F (Author) Other; Vilar, S (Author) Other; Santana, L (Author) Other; Uriarte, E (Author) Other; Hripcsak, G (Author) Other; Estrada, M (Author) Other; Rodríguez Franco, MI (Author) Other; Viña, D (Author) Other

Journal

Title: Bioorganic and Medicinal Chemistry Letters

Vol. 25

Pages: 642-648

ISSN: 0960-894X

Publisher: Elsevier

Indexing

Scopus - 18 Citations

Other information

Authenticus ID: P-00R-0N9

DOI: 10.1016/j.bmcl.2014.12.001

Abstract (EN): In this study we synthesized and evaluated a new series of amino and nitro 3-arylcoumarins as hMAO-A and hMAO-B inhibitors. Compounds 2, 3, 5 and 6 presented a better activity and selectivity profile against the hMAO-B isoform (IC<inf>50</inf> values between 2 and 6 nM) than selegiline. In general, the amino derivatives (4-6) proved to be more selective against MAO-B than the nitro derivatives (1-3). Additionally, a theoretical study of some physicochemical properties, PAMPA and reversibility assays for the most potent derivative, and molecular docking simulations were carried out to further explain the pharmacological results, and to identify the hypothetical binding mode for the compounds inside the hMAO-B.

Language: English

Type (Professor's evaluation): Scientific