title: Chalcones: a valid scaffold for monoamine oxidases inhibitors.
abstract: A large series of substituted chalcones have been synthesized and tested in vitro for their ability to inhibit human monoamine oxidases A and B (hMAO-A and hMAO-B). While all the compounds showed hMAO-B selective activity in the micro- and nanomolar ranges, the best results were obtained in the presence of chlorine and hydroxyl or methoxyl substituents. To better understand the enzyme-inhibitor interaction and to explain the selectivity of the most active compounds toward hMAO-B, molecular modeling studies were carried out on new, high resolution, hMAO-B crystallographic structures. For the only compound that also showed activity against hMAO-A as well as low selectivity, the molecular modeling study was also performed on the hMAO-A crystallographic structure. The docking technique provided new insight on the inhibition mechanism and the rational drug design of more potent/selective hMAO inhibitors based on the chalcone scaffold.
authors.affiliation: Dipartimento di Chimica e Tecnologie del Farmaco, Università degli Studi di Roma La Sapienza, P. le A. Moro 5, 00185 Roma, Italy.
authors.forename: Franco
authors.initials: F
authors.lastname: Chimenti
authors.forename: Rossella
authors.initials: R
authors.lastname: Fioravanti
authors.forename: Adriana
authors.initials: A
authors.lastname: Bolasco
authors.forename: Paola
authors.initials: P
authors.lastname: Chimenti
authors.forename: Daniela
authors.initials: D
authors.lastname: Secci
authors.forename: Francesca
authors.initials: F
authors.lastname: Rossi
authors.forename: Matilde
authors.initials: M
authors.lastname: Yáñez
authors.forename: Francisco
authors.initials: F
authors.lastname: Orallo
authors.forename: Francesco
authors.initials: F
authors.lastname: Ortuso
authors.forename: Stefano
authors.initials: S
authors.lastname: Alcaro
mesh_terms: D047188:Chalcones / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D018360:Crystallography, X-Ray; D030562:Databases, Protein; D015195:Drug Design; D006801:Humans; D020128:Inhibitory Concentration 50; D007527:Isoenzymes / Q000378:metabolism; D008958:Models, Molecular; D008995:Monoamine Oxidase / Q000378:metabolism*; D008996:Monoamine Oxidase Inhibitors / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*
chemical_list: D047188:Chalcones; D007527:Isoenzymes; D008996:Monoamine Oxidase Inhibitors; D008995:Monoamine Oxidase