MAO Inhibitory Activity of 2-Arylbenzofurans versus 3-Arylcoumarins: Synthesis, invitro Study, and Docking Calculations

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

Authors

Ferino, G (Author) Other; Cadoni, E (Author) Other; Matos, MJ (Author) Other; Elias Quezada (Author) FCUP; Uriarte, E (Author) Other; Santana, L (Author) Other; Vilar, S (Author) Other; Tatonetti, NP (Author) Other; Yanez, M (Author) Other; Vina, D (Author) Other; Picciau, C (Author) Other; Serra, S (Author) Other; Delogu, G (Author) Other

Journal

Title: ChemMedChem

Vol. 8

Pages: 956-966

ISSN: 1860-7179

Publisher: Wiley-Blackwell

Indexing

Scopus - 26 Citations

Other information

Authenticus ID: P-008-B72

DOI: 10.1002/cmdc.201300048

Abstract (EN): Monoamine oxidase (MAO) is an important drug target for the treatment of neurological disorders. Several 3-arylcoumarin derivatives were previously described as interesting selective MAO-B inhibitors. Preserving the trans-stilbene structure, a series of 2-arylbenzofuran and corresponding 3-arylcoumarin derivatives were synthesized and evaluated as inhibitors of both MAO isoforms, MAO-A and MAO-B. In general, both types of derivatives were found to be selective MAO-B inhibitors, with IC50 values in the nano- to micromolar range. 5-Nitro-2-(4-methoxyphenyl)benzofuran (8) is the most active compound of the benzofuran series, presenting MAO-B selectivity and reversible inhibition (IC50=140nM). 3-(4¿-Methoxyphenyl)-6-nitrocoumarin (15), with the same substitution pattern as that of compound 8, was found to be the most active MAO-B inhibitor of the coumarin series (IC50=3nM). However, 3-phenylcoumarin 14 showed activity in the same range (IC50=6nM), is reversible, and also severalfold more selective than compound 15. Docking experiments for the most active compounds into the MAO-B and MAO-A binding pockets highlighted different interactions between the derivative classes (2-arylbenzofurans and 3-arylcoumarins), and provided new information about the enzyme-inhibitor interaction and the potential therapeutic application of these scaffolds. © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Language: English

Type (Professor's evaluation): Scientific