title: Hydroxycoumarins as selective MAO-B inhibitors.
abstract: A series of 3-aryl-4-hydroxycoumarin derivatives was synthesized with the aim to find out the structural features for the MAO inhibitory activity and selectivity. Methoxy and/or chloro substituents were introduced in the 3-phenyl ring, whereas the position 6 in the coumarin moiety was not substituted or substituted with a methyl group or a chloro atom due to their different electronic, steric and/or lipophilic properties. Most of the synthesized compounds presented MAO-B inhibitory activity. The presence of methoxy and chloro groups, respectively in the para and meta positions of the 3-phenyl ring, have an important influence on the inhibitory activity. Moreover, the presence of a chloro atom in the six position of the moiety (compound 7) improved the inhibitor activity as well as its selectivity against MAO-B compared with iproniazide, used as reference compound. Docking experiments were carried out to understand which are the most energetically preferred orientations adopted by compounds 5, 6 and 7 inside the MAO-B binding pocket.
authors.affiliation: Dipartimento Farmaco Chimico Tecnologico, Università degli Studi di Cagliari, Via Ospedale 72, 09124 Cagliari, Italy. silvserra@tiscali.it
authors.forename: Silvia
authors.initials: S
authors.lastname: Serra
authors.forename: Giulio
authors.initials: G
authors.lastname: Ferino
authors.forename: Maria João
authors.initials: MJ
authors.lastname: Matos
authors.forename: Saleta
authors.initials: S
authors.lastname: Vázquez-Rodríguez
authors.forename: Giovanna
authors.initials: G
authors.lastname: Delogu
authors.forename: Dolores
authors.initials: D
authors.lastname: Viña
authors.forename: Enzo
authors.initials: E
authors.lastname: Cadoni
authors.forename: Lourdes
authors.initials: L
authors.lastname: Santana
authors.forename: Eugenio
authors.initials: E
authors.lastname: Uriarte
mesh_terms: D015110:4-Hydroxycoumarins / Q000494:pharmacology*; D000818:Animals; D001386:Azides / Q000494:pharmacology; D001665:Binding Sites; D002626:Chemistry, Pharmaceutical / Q000379:methods*; D003198:Computer Simulation; D015195:Drug Design; D006801:Humans; D020128:Inhibitory Concentration 50; D009682:Magnetic Resonance Spectroscopy; D008956:Models, Chemical; D008995:Monoamine Oxidase / Q000737:chemistry*; D008996:Monoamine Oxidase Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology*; D055672:Static Electricity; D013329:Structure-Activity Relationship; D013816:Thermodynamics
chemical_list: D015110:4-Hydroxycoumarins; D001386:Azides; D008996:Monoamine Oxidase Inhibitors; D008995:Monoamine Oxidase