title: Through scaffold modification to 3,5-diaryl-4,5-dihydroisoxazoles: new potent and selective inhibitors of monoamine oxidase B.
abstract: 3,5-Diaryl-4,5-dihydroisoxazoles were synthesized and evaluated as monoamine oxidase (MAO) enzyme inhibitors and iron chelators. All compounds exhibited selective inhibitory activity towards the B isoform of MAO in the nanomolar concentration range. The best performing compound was preliminarily evaluated for its ability to bind iron II and III cations, indicating that neither iron II nor iron III is coordinated. The best compounds racemic mixtures were separated and single enantiomers inhibitory activity evaluated. Furthermore, none of the synthesised compounds exhibited activity towards MAO A. Overall, these data support our hypothesis that 3,5-diaryl-4,5-dihydroisoxazoles are promising scaffolds for the design of neuroprotective agents.
authors.affiliation: a Department of Life and Environmental Sciences , University of Cagliari , Cagliari , Italy.
authors.forename: Rita
authors.initials: R
authors.lastname: Meleddu
authors.affiliation: a Department of Life and Environmental Sciences , University of Cagliari , Cagliari , Italy.
authors.forename: Simona
authors.initials: S
authors.lastname: Distinto
authors.affiliation: b Dipartimento del Farmaco , Istituto Superiore di Sanità , Rome , Italy.
authors.forename: Roberto
authors.initials: R
authors.lastname: Cirilli
authors.affiliation: c Dipartimento di Scienze della Salute , Università Magna Græcia di Catanzaro , Catanzaro , Italy.
authors.forename: Stefano
authors.initials: S
authors.lastname: Alcaro
authors.affiliation: d Departamento de Farmacología and Instituto de Farmacia Industrial , Universidad de Santiago de Compostela, Campus Universitario Sur , Santiago de Compostela , Spain.
authors.forename: Matilde
authors.initials: M
authors.lastname: Yanez
authors.affiliation: a Department of Life and Environmental Sciences , University of Cagliari , Cagliari , Italy.
authors.forename: Maria Luisa
authors.initials: ML
authors.lastname: Sanna
authors.affiliation: a Department of Life and Environmental Sciences , University of Cagliari , Cagliari , Italy.
authors.forename: Angela
authors.initials: A
authors.lastname: Corona
authors.affiliation: a Department of Life and Environmental Sciences , University of Cagliari , Cagliari , Italy.
authors.forename: Claudia
authors.initials: C
authors.lastname: Melis
authors.affiliation: a Department of Life and Environmental Sciences , University of Cagliari , Cagliari , Italy.
authors.forename: Giulia
authors.initials: G
authors.lastname: Bianco
authors.affiliation: e Department of Organic Chemistry , Semmelweis University , Budapest , Hungary.
authors.forename: Peter
authors.initials: P
authors.lastname: Matyus
authors.affiliation: a Department of Life and Environmental Sciences , University of Cagliari , Cagliari , Italy.
authors.forename: Filippo
authors.initials: F
authors.lastname: Cottiglia
authors.affiliation: a Department of Life and Environmental Sciences , University of Cagliari , Cagliari , Italy.
authors.forename: Elias
authors.initials: E
authors.lastname: Maccioni
mesh_terms: D007555:Isoxazoles / Q000737:chemistry / Q000494:pharmacology*; D008958:Models, Molecular; D008995:Monoamine Oxidase / Q000378:metabolism*; D008996:Monoamine Oxidase Inhibitors / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship
chemical_list: D007555:Isoxazoles; D008996:Monoamine Oxidase Inhibitors; D008995:Monoamine Oxidase
keywords: 3,5-diaryl-dihydroisoxazoles; MAO B selective inhibitors; neuroprotective agents