title: (E)-3-Heteroarylidenechroman-4-ones as potent and selective monoamine oxidase-B inhibitors.
abstract: A series of (E)-3-heteroarylidenechroman-4-ones (1a-r) was designed, synthesized and investigated in vitro for their ability to inhibit the enzymatic activity of both human monoamine oxidase (hMAO) isoforms, hMAO-A and hMAO-B. All the compounds were found to be selective hMAO-B inhibitors showing IC50 values in the nanomolar or micromolar range. (E)-5,7-Dichloro-3-{[(2-(dimethylamino)pyrimidin-5-yl]methylene}chroman-4-one (1c) was the most interesting compound identified in this study, endowed with higher hMAO-B potency (IC50 = 10.58 nM) and selectivity (SI > 9452) with respect to the reference selective inhibitor selegiline (IC50 = 19.60 nM, IC50 > 3431). Molecular modelling studies were performed for rationalizing at molecular level the target selective inhibition of our compounds, revealing a remarkable contribution of hydrogen bond network and water solvent.
authors.affiliation: Dipartimento di Chimica e Tecnologie del Farmaco, Sapienza - Università di Roma, P.le Aldo Moro, 5, 00185, Rome, Italy. Electronic address: nicoletta.desideri@uniroma1.it.
authors.forename: Nicoletta
authors.initials: N
authors.lastname: Desideri
authors.affiliation: Dipartimento di Chimica e Tecnologie del Farmaco, Sapienza - Università di Roma, P.le Aldo Moro, 5, 00185, Rome, Italy.
authors.forename: Luca
authors.initials: L
authors.lastname: Proietti Monaco
authors.affiliation: Dipartimento di Chimica e Tecnologie del Farmaco, Sapienza - Università di Roma, P.le Aldo Moro, 5, 00185, Rome, Italy.
authors.forename: Rossella
authors.initials: R
authors.lastname: Fioravanti
authors.affiliation: Dipartimento di Chimica e Tecnologie del Farmaco, Sapienza - Università di Roma, P.le Aldo Moro, 5, 00185, Rome, Italy.
authors.forename: Mariangela
authors.initials: M
authors.lastname: Biava
authors.affiliation: Departamento de Farmacología, Facultad de Farmacia, Universidad de Santiago de Compostela, Campus Universitario Sur, E-15782, Santiago de Compostela (La Coruña), Spain.
authors.forename: Matilde
authors.initials: M
authors.lastname: Yáñez
authors.affiliation: Dipartimento di Scienze della Salute, Università"Magna Græcia" di Catanzaro, Campus Universitario "S. Venuta", Viale Europa, 88100, Catanzaro, Italy.
authors.forename: Stefano
authors.initials: S
authors.lastname: Alcaro
authors.affiliation: Dipartimento di Scienze della Salute, Università"Magna Græcia" di Catanzaro, Campus Universitario "S. Venuta", Viale Europa, 88100, Catanzaro, Italy.
authors.forename: Francesco
authors.initials: F
authors.lastname: Ortuso
mesh_terms: D002839:Chromans / Q000737:chemistry* / Q000494:pharmacology; D006801:Humans; D006860:Hydrogen Bonding; D020128:Inhibitory Concentration 50; D008958:Models, Molecular; D008995:Monoamine Oxidase / Q000187:drug effects; D008996:Monoamine Oxidase Inhibitors / Q000737:chemistry* / Q000494:pharmacology; D012680:Sensitivity and Specificity; D012997:Solvents / Q000494:pharmacology; D013329:Structure-Activity Relationship
chemical_list: D002839:Chromans; D008996:Monoamine Oxidase Inhibitors; D012997:Solvents; D008995:Monoamine Oxidase
keywords: Chroman-4-ones; Docking studies; Homoisoflavonoids; Monoamine oxidases; Selective hMAO-B inhibitors