title: MAO inhibitory activity of 2-arylbenzofurans versus 3-arylcoumarins: synthesis, in vitro study, and docking calculations.
abstract: 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 =140 nM). 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 =3 nM). However, 3-phenylcoumarin 14 showed activity in the same range (IC50 =6 nM), 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.
authors.affiliation: Department of Chemical and Geological Sciences, University of Cagiari, Monserrato Cagliari, Italy.
authors.forename: Giulio
authors.initials: G
authors.lastname: Ferino
authors.forename: Enzo
authors.initials: E
authors.lastname: Cadoni
authors.forename: Maria João
authors.initials: MJ
authors.lastname: Matos
authors.forename: Elias
authors.initials: E
authors.lastname: Quezada
authors.forename: Eugenio
authors.initials: E
authors.lastname: Uriarte
authors.forename: Lourdes
authors.initials: L
authors.lastname: Santana
authors.forename: Santiago
authors.initials: S
authors.lastname: Vilar
authors.forename: Nicholas P
authors.initials: NP
authors.lastname: Tatonetti
authors.forename: Matilde
authors.initials: M
authors.lastname: Yáñez
authors.forename: Dolores
authors.initials: D
authors.lastname: Viña
authors.forename: Carmen
authors.initials: C
authors.lastname: Picciau
authors.forename: Silvia
authors.initials: S
authors.lastname: Serra
authors.forename: Giovanna
authors.initials: G
authors.lastname: Delogu
mesh_terms: D001572:Benzofurans / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D003374:Coumarins / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D008958:Models, Molecular; D015394:Molecular Structure; D008995:Monoamine Oxidase / Q000378:metabolism*; D013329:Structure-Activity Relationship
chemical_list: D001572:Benzofurans; D003374:Coumarins; D004791:Enzyme Inhibitors; D008995:Monoamine Oxidase