title: Inhibition of monoamine oxidases by coumarin-3-acyl derivatives: biological activity and computational study.
abstract: A series of coumarin-3-acyl derivatives have been synthesized and investigated for the ability to inhibit selectively monoamine oxidases. The coumarin-3-carboxylic acids, 2a-e, proved to be reversible and selective inhibitors of the MAO-B isoform, displaying pIC(50) values of particular interest: 2a shows pIC(50) 7.76 and a selectivity index (pS.I.) 2.94 and 2b shows pIC(50) 7.72 and a pS.I. of 2.80. The coumarin-3-acyl chlorides 3a-e showed high pIC(50) values against both MAO-A and MAO-B isoforms, 3d being the highest against MAO-B with a pIC(50) value of 8.00. In order to rationalize the activity/selectivity results, molecular descriptors were generated. Further insight about enzyme-inhibitor interaction was obtained by docking experiments with the MAO-B isoform.
authors.affiliation: Dipartimento di Studi di Chimica e Tecnologia delle Sostanze Biologicamente Attive, Università degli Studi di Roma 'La Sapienza', P.le A. Moro 5, 00185 Rome, Italy.
authors.forename: Franco
authors.initials: F
authors.lastname: Chimenti
authors.forename: Daniela
authors.initials: D
authors.lastname: Secci
authors.forename: Adriana
authors.initials: A
authors.lastname: Bolasco
authors.forename: Paola
authors.initials: P
authors.lastname: Chimenti
authors.forename: Arianna
authors.initials: A
authors.lastname: Granese
authors.forename: Olivia
authors.initials: O
authors.lastname: Befani
authors.forename: Paola
authors.initials: P
authors.lastname: Turini
authors.forename: Stefano
authors.initials: S
authors.lastname: Alcaro
authors.forename: Francesco
authors.initials: F
authors.lastname: Ortuso
mesh_terms: D006631:Amine Oxidase (Copper-Containing) / Q000037:antagonists & inhibitors / Q000378:metabolism*; D000818:Animals; D001665:Binding Sites / Q000187:drug effects; D001921:Brain / Q000187:drug effects / Q000201:enzymology; D002460:Cell Line; D019295:Computational Biology; D003374:Coumarins / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D020128:Inhibitory Concentration 50; D008968:Molecular Conformation; D008996:Monoamine Oxidase Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology; D013329:Structure-Activity Relationship
chemical_list: D003374:Coumarins; D008996:Monoamine Oxidase Inhibitors; D006631:Amine Oxidase (Copper-Containing); C104227:coumarin-3-carboxylic acid