title: Design, synthesis and biological activity of multifunctional α,β-unsaturated carbonyl scaffolds for Alzheimer's disease.
abstract: A series of compounds containing an α,β-unsaturated carbonyl moiety, such as chalcones and coumarins were designed, synthesized and tested in a variety of assays to assess their potential as anti-Alzheimer's disease (AD) agents. The investigations included the inhibition of cholinesterases (AChE, BuChE), the inhibition of amyloid beta (Aβ) self-assembly and the disassembly of preformed Aβ oligomers. Several compounds showed excellent potential as multifunctional compounds for AD. Docking studies for 16 that performed well in all the assays gave a clear interpretation of various interactions in the gorge of AChE. Based on the results, the long-chain coumarin scaffold appears to be a promising structural template for further AD drug development.
authors.affiliation: Department of Chemistry, University of Massachusetts Boston, 100 Morrissey Blvd, Boston, MA 02125-3393, USA.
authors.forename: Seema
authors.initials: S
authors.lastname: Bag
authors.forename: Sanjukta
authors.initials: S
authors.lastname: Ghosh
authors.forename: Rekha
authors.initials: R
authors.lastname: Tulsan
authors.forename: Abha
authors.initials: A
authors.lastname: Sood
authors.forename: Weihong
authors.initials: W
authors.lastname: Zhou
authors.forename: Christine
authors.initials: C
authors.lastname: Schifone
authors.forename: Michelle
authors.initials: M
authors.lastname: Foster
authors.forename: Harry
authors.initials: H
authors.lastname: LeVine
authors.forename: Béla
authors.initials: B
authors.lastname: Török
authors.forename: Marianna
authors.initials: M
authors.lastname: Török
mesh_terms: D000110:Acetylcholinesterase / Q000737:chemistry / Q000378:metabolism; D000544:Alzheimer Disease / Q000188:drug therapy; D016229:Amyloid beta-Peptides / Q000037:antagonists & inhibitors / Q000378:metabolism; D001665:Binding Sites; D020134:Catalytic Domain; D047188:Chalcones / Q000138:chemical synthesis / Q000737:chemistry* / Q000627:therapeutic use; D002800:Cholinesterase Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000627:therapeutic use; D003374:Coumarins / Q000138:chemical synthesis / Q000737:chemistry* / Q000627:therapeutic use; D015195:Drug Design; D006801:Humans; D062105:Molecular Docking Simulation; D013329:Structure-Activity Relationship
chemical_list: D016229:Amyloid beta-Peptides; D047188:Chalcones; D002800:Cholinesterase Inhibitors; D003374:Coumarins; C030123:coumarin; D000110:Acetylcholinesterase
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