Novel (coumarin-3-yl)carbamates as selective MAO-B inhibitors: Synthesis, in vitro and in vivo assays, theoretical evaluation of ADME properties and docking study

• Type: Article in International Scientific Journal
• Date: 2013

Authors

Matos, MJ (Author) Other; Vilar, S (Author) Other; Gonzalez Franco, RM (Author) Other; Uriarte, E (Author) Other; Santana, L (Author) Other; Friedman, C (Author) Other; Tatonetti, NP (Author) Other; Viña, D (Author) Other; Fontenla, JA (Author) Other

Journal

Title: European Journal of Medicinal Chemistry

Vol. 63

Pages: 151-161

ISSN: 0223-5234

Publisher: Elsevier

Indexing

Scopus - 35 Citations

Other information

Authenticus ID: P-00R-0MW

DOI: 10.1016/j.ejmech.2013.02.009

Abstract (EN): A series of (coumarin-3-yl)carbamates was synthesized and evaluated in vitro as monoamine oxidase (MAO-A and MAO-B) inhibitors. Most of the new compounds selectively inhibited MAO-B isoenzyme with IC50 values in the micro or nanoMolar ranges. Since these compounds must achieve the brain cells, theoretical evaluation of ADME properties were also carried out. Compound 8 (benzyl(coumarin-3-yl)carbamate), which presented the most interesting in vitro MAO-B inhibitory profile (IC50 against MAO-B = 45 nM), was subjected to further studies. This in vitro MAO-B inhibitory activity is comparable with that of the selegiline, the reference compound (IC50 against MAO-B = 20 nM). Taking into account the in vitro results of compound 8, in vivo assays and docking calculations were also carried out for this derivative.

Language: English

Type (Professor's evaluation): Scientific