title: Synthesis and evaluation of novel 1,2,3-triazole-based acetylcholinesterase inhibitors with neuroprotective activity.
abstract: A series of new 1,2,3-triazole derivatives were synthesized and evaluated for anticholinesterase and neuroprotective activities. Some synthetic derivatives, especially compound 32, exhibited improved acetylcholinesterase (AChE) inhibitory activity by comparison with the hit 1, high selectivity toward AChE over butyrylcholinesterase (BuChE), and suitable in vitro neuroprotective effect against amyloid-β25-35 (Aβ25-35)-induced neurotoxicity in SH-SY5Y cells. Furthermore, these molecules have desired physicochemical properties in the range of CNS drugs and showed no cytotoxicity against two normal cells, including human keratinocytes HaCaT and murine fibroblasts NIH-3T3. The preliminary bioassay results and docking study indicated that compound 32 might be a promising lead compound with dual action for the treatment of Alzheimer's disease.
authors.affiliation: Department of Pharmaceutical Engineering, School of Biological Science and Technology, University of Jinan, Jinan 250022, China.
authors.forename: Jia-Cheng
authors.initials: JC
authors.lastname: Li
authors.affiliation: Institute of Biological Sciences, University of Brasília, Brasilia 70910900, Brazil.
authors.forename: Juan
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Institute of Biological Sciences, University of Brasília, Brasilia 70910900, Brazil.
authors.forename: Mosar Corrêa
authors.initials: MC
authors.lastname: Rodrigues
authors.affiliation: College of Pharmacy, Weifang Medical University, Weifang 261042, China.
authors.forename: De-Jun
authors.initials: DJ
authors.lastname: Ding
authors.affiliation: Institute of Biological Sciences, University of Brasília, Brasilia 70910900, Brazil.
authors.forename: João Paulo Figueiró
authors.initials: JP
authors.lastname: Longo
authors.affiliation: Institute of Biological Sciences, University of Brasília, Brasilia 70910900, Brazil.
authors.forename: Ricardo Bentes
authors.initials: RB
authors.lastname: Azevedo
authors.affiliation: Institute of Biological Sciences, University of Brasília, Brasilia 70910900, Brazil; Faculty of Ceilandia, University of Brasilia, Brasilia 72220-900, Brazil.
authors.forename: Luis Alexandre
authors.initials: LA
authors.lastname: Muehlmann
authors.affiliation: Department of Pharmaceutical Engineering, School of Biological Science and Technology, University of Jinan, Jinan 250022, China. Electronic address: jiangchengshi-20@163.com.
authors.forename: Cheng-Shi
authors.initials: CS
authors.lastname: Jiang
mesh_terms: D000110:Acetylcholinesterase / Q000737:chemistry / Q000378:metabolism; D016229:Amyloid beta-Peptides / Q000633:toxicity; D000818:Animals; D001665:Binding Sites; D001812:Blood-Brain Barrier / Q000378:metabolism; D002091:Butyrylcholinesterase / Q000737:chemistry / Q000378:metabolism; D020134:Catalytic Domain; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D002800:Cholinesterase Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D006801:Humans; D006860:Hydrogen Bonding; D051379:Mice; D062105:Molecular Docking Simulation; D041681:NIH 3T3 Cells; D018696:Neuroprotective Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D010446:Peptide Fragments / Q000633:toxicity; D014230:Triazoles / Q000138:chemical synthesis / Q000737:chemistry*
chemical_list: D016229:Amyloid beta-Peptides; D002800:Cholinesterase Inhibitors; D018696:Neuroprotective Agents; D010446:Peptide Fragments; D014230:Triazoles; C074636:amyloid beta-protein (25-35); D000110:Acetylcholinesterase; D002091:Butyrylcholinesterase
keywords: 1,2,3-Triazole; Acetylcholinesterase; Alzheimer’s disease; Amyloid-β-peptide; Neuroprotective