title: Design and synthesis of novel chalcones as potent selective monoamine oxidase-B inhibitors.
abstract: A novel series of substituted chalcones were designed and synthesized to be evaluated as selective human MAO-B inhibitors. A combination of either methylsulfonyl or trifluoromethyl substituents on the aromatic ketone moiety with a benzodioxol ring on the other end of the chalcone scaffold was investigated. The compounds were tested for their inhibitory activities on both human MAO-A and B. All compounds appeared to be selective MAO-B inhibitors with Ki values in the micromolar to submicromolar range. Molecular modeling studies have been performed to get insight into the binding mode of the synthesized compounds to human MAO-B active site.
authors.affiliation: College of Pharmacy, Qatar University, Doha, Qatar.
authors.forename: Arwa
authors.initials: A
authors.lastname: Hammuda
authors.affiliation: College of Pharmacy, Qatar University, Doha, Qatar.
authors.forename: Raed
authors.initials: R
authors.lastname: Shalaby
authors.affiliation: Department of Biology and Biotechnology, University of Pavia, Via Ferrata 1, 27100, Pavia, Italy.
authors.forename: Stefano
authors.initials: S
authors.lastname: Rovida
authors.affiliation: Department of Biochemistry, Emory University School of Medicine, Atlanta, GA, 30322, USA.
authors.forename: Dale E
authors.initials: DE
authors.lastname: Edmondson
authors.affiliation: Department of Biology and Biotechnology, University of Pavia, Via Ferrata 1, 27100, Pavia, Italy.
authors.forename: Claudia
authors.initials: C
authors.lastname: Binda
authors.affiliation: College of Pharmacy, Qatar University, Doha, Qatar. Electronic address: akhalil@qu.edu.qa.
authors.forename: Ashraf
authors.initials: A
authors.lastname: Khalil
mesh_terms: D047188:Chalcones / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D015195:Drug Design; D006801:Humans; D062105:Molecular Docking Simulation; D015394:Molecular Structure; D008995:Monoamine Oxidase / Q000378:metabolism*; D008996:Monoamine Oxidase Inhibitors / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D013329:Structure-Activity Relationship
chemical_list: D047188:Chalcones; D008996:Monoamine Oxidase Inhibitors; D008995:Monoamine Oxidase
keywords: Chalcones; Drug design; Enzyme; Monoamine oxidase; Neuroprotection; Synthesis