title: Synthesis and application of β-carbolines as novel multi-functional anti-Alzheimer's disease agents.
abstract: The design, synthesis and assessment of β-carboline core-based compounds as potential multifunctional agents against several processes that are believed to play a significant role in Alzheimer's disease (AD) pathology, are described. The activity of the compounds was determined in Aβ self-assembly (fibril and oligomer formation) and cholinesterase (AChE, BuChE) activity inhibition, and their antioxidant properties were also assessed. To obtain insight into the mode of action of the compounds, HR-MS studies were carried out on the inhibitor-Aβ complex formation and molecular docking was performed on inhibitor-BuChE interactions. While several compounds exhibited strong activities in individual assays, compound 14 emerged as a promising multi-target lead for the further structure-activity relationship studies.
authors.affiliation: University of Massachusetts Boston, 100 Morrissey Blvd., Boston, MA, USA.
authors.forename: William
authors.initials: W
authors.lastname: Horton
authors.affiliation: University of Massachusetts Boston, 100 Morrissey Blvd., Boston, MA, USA.
authors.forename: Abha
authors.initials: A
authors.lastname: Sood
authors.affiliation: University of Massachusetts Boston, 100 Morrissey Blvd., Boston, MA, USA.
authors.forename: Swarada
authors.initials: S
authors.lastname: Peerannawar
authors.affiliation: University of Massachusetts Boston, 100 Morrissey Blvd., Boston, MA, USA.
authors.forename: Nandor
authors.initials: N
authors.lastname: Kugyela
authors.affiliation: University of Massachusetts Boston, 100 Morrissey Blvd., Boston, MA, USA.
authors.forename: Aditya
authors.initials: A
authors.lastname: Kulkarni
authors.affiliation: University of Massachusetts Boston, 100 Morrissey Blvd., Boston, MA, USA.
authors.forename: Rekha
authors.initials: R
authors.lastname: Tulsan
authors.affiliation: University of Massachusetts Boston, 100 Morrissey Blvd., Boston, MA, USA.
authors.forename: Chris D
authors.initials: CD
authors.lastname: Tran
authors.affiliation: University of Massachusetts Boston, 100 Morrissey Blvd., Boston, MA, USA.
authors.forename: Jessica
authors.initials: J
authors.lastname: Soule
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: University of Massachusetts Boston, 100 Morrissey Blvd., Boston, MA, USA.
authors.forename: Béla
authors.initials: B
authors.lastname: Török
authors.affiliation: 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: D000544:Alzheimer Disease / Q000188:drug therapy* / Q000378:metabolism; D016229:Amyloid beta-Peptides / Q000032:analysis* / Q000096:biosynthesis; D000975:Antioxidants / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D002243:Carbolines / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D002800:Cholinesterase Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D002802:Cholinesterases / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D015195:Drug Design; D006801:Humans; D062105:Molecular Docking Simulation; D015394:Molecular Structure; D013329:Structure-Activity Relationship
chemical_list: D016229:Amyloid beta-Peptides; D000975:Antioxidants; D002243:Carbolines; D002800:Cholinesterase Inhibitors; D002802:Cholinesterases
keywords: Alzheimer’s disease; Amyloid beta; Antioxidant; Cholinesterase inhibition; β-Carbolines