title: Chromone 3-phenylcarboxamides as potent and selective MAO-B inhibitors.
abstract: Monoamine oxidase (MAO) is an enzyme, present in mammals in two isoforms MAO-A and MAO-B. These isoforms have a crucial role in neurotransmitters metabolism, representing an attractive drug target in the therapy of neurodegenerative diseases (MAO-B) and depression (MAO-A). In this context, our work has been focused on the discovery of new chemical entities (NCEs) for MAO inhibition, based on the development of chromone carboxamides. Chromone derivatives with a carboxamide function located in position 2- and 3- of the benzo-γ-pyrone core, (compounds 2-6 and 8-12) were synthesized, with moderate/good yields, by a one-pot condensation reaction using phosphonium salts as coupling reagents. The synthetic compounds were screened towards human MAO isoforms (hMAO) to evaluate their potency and selectivity. The chromone-3-carboxamides show high selectivity to hMAO-B, with compounds 9 and 12 displaying IC(50) values at nanomolar range.
authors.affiliation: CIQ/Departamento de Química e Bioquímica, Faculdade de Ciências, Universidade do Porto, 4169-007 Porto, Portugal.
authors.forename: Alexandra
authors.initials: A
authors.lastname: Gaspar
authors.forename: Joana
authors.initials: J
authors.lastname: Reis
authors.forename: André
authors.initials: A
authors.lastname: Fonseca
authors.forename: Nuno
authors.initials: N
authors.lastname: Milhazes
authors.forename: Dolores
authors.initials: D
authors.lastname: Viña
authors.forename: Eugenio
authors.initials: E
authors.lastname: Uriarte
authors.forename: Fernanda
authors.initials: F
authors.lastname: Borges
mesh_terms: D000818:Animals; D002460:Cell Line; D002867:Chromones / Q000737:chemistry* / Q000494:pharmacology*; D006801:Humans; D020128:Inhibitory Concentration 50; D008958:Models, Molecular; D008995:Monoamine Oxidase / Q000378:metabolism*; D008996:Monoamine Oxidase Inhibitors / Q000737:chemistry* / Q000494:pharmacology*; D019636:Neurodegenerative Diseases / Q000188:drug therapy / Q000201:enzymology; D020033:Protein Isoforms / Q000037:antagonists & inhibitors / Q000378:metabolism; D013329:Structure-Activity Relationship
chemical_list: D002867:Chromones; D008996:Monoamine Oxidase Inhibitors; D020033:Protein Isoforms; D008995:Monoamine Oxidase