title: Sulfonamides as multifunctional agents for Alzheimer's disease.
abstract: Sulfonamide linker-based inhibitors with extended linear structure were designed and synthesized with the aim of producing multifunctional agents against several processes involved in the pathology of Alzheimer's disease (AD). The potency of the compounds were assessed in the inhibition of Aβ self-assembly (fibril and oligomer formation), in modulating cholinesterase (AChE, BuChE) activity, and scavenging free radicals. Several compounds exhibited promising Aβ self-assembly and cholinesterase inhibition and in parallel, showed good free radical scavenging properties. The investigation of the scaffold described in this study resulted in the identification of three compounds (14, 19 and 26) as promising leads for the further design of multifunctional drug candidates for AD.
authors.affiliation: Department of Chemistry, University of Massachusetts Boston, 100 Morrissey Blvd., Boston, MA, USA.
authors.forename: Seema
authors.initials: S
authors.lastname: Bag
authors.affiliation: Department of Chemistry, University of Massachusetts Boston, 100 Morrissey Blvd., Boston, MA, USA.
authors.forename: Rekha
authors.initials: R
authors.lastname: Tulsan
authors.affiliation: Department of Chemistry, University of Massachusetts Boston, 100 Morrissey Blvd., Boston, MA, USA.
authors.forename: Abha
authors.initials: A
authors.lastname: Sood
authors.affiliation: Department of Chemistry, University of Massachusetts Boston, 100 Morrissey Blvd., Boston, MA, USA.
authors.forename: Hyejin
authors.initials: H
authors.lastname: Cho
authors.affiliation: Department of Chemistry, University of Massachusetts Boston, 100 Morrissey Blvd., Boston, MA, USA.
authors.forename: Hana
authors.initials: H
authors.lastname: Redjeb
authors.affiliation: Department of Chemistry, University of Massachusetts Boston, 100 Morrissey Blvd., Boston, MA, USA.
authors.forename: Weihong
authors.initials: W
authors.lastname: Zhou
authors.affiliation: Department of Molecular and Cellular Biochemistry, Chandler School of Medicine, and Center on Aging, University of Kentucky, Lexington, KY 40536, USA.
authors.forename: Harry
authors.initials: H
authors.lastname: LeVine
authors.affiliation: Department of Chemistry, University of Massachusetts Boston, 100 Morrissey Blvd., Boston, MA, USA. Electronic address: bela.torok@umb.edu.
authors.forename: Béla
authors.initials: B
authors.lastname: Török
authors.affiliation: Department of Chemistry, University of Massachusetts Boston, 100 Morrissey Blvd., Boston, MA, USA. Electronic address: marianna.torok@umb.edu.
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; D002091:Butyrylcholinesterase / Q000737:chemistry / Q000378:metabolism; D020134:Catalytic Domain; D002800:Cholinesterase Inhibitors / Q000737:chemistry* / Q000378:metabolism / Q000627:therapeutic use; D000077265:Donepezil; D016166:Free Radical Scavengers / Q000737:chemistry* / Q000378:metabolism / Q000627:therapeutic use; D006801:Humans; D007189:Indans / Q000737:chemistry / Q000378:metabolism; D056004:Molecular Dynamics Simulation; D010880:Piperidines / Q000737:chemistry / Q000378:metabolism; D011485:Protein Binding; D013449:Sulfonamides / Q000737:chemistry* / Q000378:metabolism / Q000627:therapeutic use
chemical_list: D016229:Amyloid beta-Peptides; D002800:Cholinesterase Inhibitors; D016166:Free Radical Scavengers; D007189:Indans; D010880:Piperidines; D013449:Sulfonamides; D000077265:Donepezil; D000110:Acetylcholinesterase; D002091:Butyrylcholinesterase
keywords: Alzheimer’s disease; Amyloid-β; Antioxidant; Cholinesterase inhibition; Sulfonamides