1452849-95-4Relevant academic research and scientific papers
MAO Inhibitory Activity of 2-Arylbenzofurans versus 3-Arylcoumarins: Synthesis, invitro Study, and Docking Calculations
Ferino, Giulio,Cadoni, Enzo,Matos, Maria Joao,Quezada, Elias,Uriarte, Eugenio,Santana, Lourdes,Vilar, Santiago,Tatonetti, Nicholas P.,Yanez, Matilde,Vina, Dolores,Picciau, Carmen,Serra, Silvia,Delogu, Giovanna
, p. 956 - 966 (2013/07/27)
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.
