title: 3-Acetyl-2,5-diaryl-2,3-dihydro-1,3,4-oxadiazoles: a new scaffold for the selective inhibition of monoamine oxidase B.
abstract: 3-Acetyl-2,5-diaryl-2,3-dihydro-1,3,4-oxadiazoles were designed, synthesized, and tested as inhibitors against human monoamine oxidase (MAO) A and B isoforms. Several compounds, obtained as racemates, were identified as selective MAO-B inhibitors. The enantiomers of some derivatives were separated by enantioselective HPLC and tested. The R-enantiomers always showed the highest activity. Docking study and molecular dynamic simulations demonstrated the putative binding mode. We conclude that these 1,3,4-oxadiazoles derivatives are promising reversible and selective MAO-B inhibitors.
authors.affiliation: Dipartimento Farmaco Chimico Tecnologico, University of Cagliari, Via Ospedale 72, 09124, Cagliari, Italy.
authors.forename: Elias
authors.initials: E
authors.lastname: Maccioni
authors.forename: Stefano
authors.initials: S
authors.lastname: Alcaro
authors.forename: Roberto
authors.initials: R
authors.lastname: Cirilli
authors.forename: Sara
authors.initials: S
authors.lastname: Vigo
authors.forename: Maria Cristina
authors.initials: MC
authors.lastname: Cardia
authors.forename: Maria Luisa
authors.initials: ML
authors.lastname: Sanna
authors.forename: Rita
authors.initials: R
authors.lastname: Meleddu
authors.forename: Matilde
authors.initials: M
authors.lastname: Yanez
authors.forename: Giosuè
authors.initials: G
authors.lastname: Costa
authors.forename: Laura
authors.initials: L
authors.lastname: Casu
authors.forename: Peter
authors.initials: P
authors.lastname: Matyus
authors.forename: Simona
authors.initials: S
authors.lastname: Distinto
mesh_terms: D000818:Animals; D002460:Cell Line; D015195:Drug Design; D006801:Humans; D007313:Insecta / Q000166:cytology; D007527:Isoenzymes / Q000037:antagonists & inhibitors; D008958:Models, Molecular; D008996:Monoamine Oxidase Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D010069:Oxadiazoles / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D011485:Protein Binding; D011994:Recombinant Proteins / Q000037:antagonists & inhibitors; D013237:Stereoisomerism; D013329:Structure-Activity Relationship
chemical_list: D007527:Isoenzymes; D008996:Monoamine Oxidase Inhibitors; D010069:Oxadiazoles; D011994:Recombinant Proteins