title: Synthesis and anti-acetylcholinesterase activity of scopoletin derivatives.
abstract: A series of scopoletin derivatives incorporated with the pyridinium moiety was synthesized and evaluated for their acetylcholinesterase (AChE) inhibitory activity by the colorimetric Ellman's method. A 2-fluorobenzylpyridinium derivative was the most potent among the tested compounds, with an IC50 value of 0.215±0.015μM, which was greatly improved from that of scopoletin. Docking studies revealed that the scopoletin portion of the mentioned compound was bound to the peripheral anionic site of the AChE, whereas the N-benzylpyridinium residue to the catalytic anionic site.
authors.affiliation: Laboratory of Organic Synthesis, Chulabhorn Research Institute, 54 Kamphaeng Phet 6, Talat Bang Khen, Lak Si, Bangkok 10210, Thailand.
authors.forename: Nisachon
authors.initials: N
authors.lastname: Khunnawutmanotham
authors.affiliation: Laboratory of Natural Products, Chulabhorn Research Institute, 54 Kamphaeng Phet 6, Talat Bang Khen, Lak Si, Bangkok 10210, Thailand.
authors.forename: Nitirat
authors.initials: N
authors.lastname: Chimnoi
authors.affiliation: Department of Chemistry, Faculty of Science, Kasetsart University, Bangkok 10900, Thailand.
authors.forename: Patchreenart
authors.initials: P
authors.lastname: Saparpakorn
authors.affiliation: Laboratory of Organic Synthesis, Chulabhorn Research Institute, 54 Kamphaeng Phet 6, Talat Bang Khen, Lak Si, Bangkok 10210, Thailand; Department of Chemistry, Faculty of Science, Kasetsart University, Bangkok 10900, Thailand. Electronic address: fscispt@ku.ac.th.
authors.forename: Supanna
authors.initials: S
authors.lastname: Techasakul
mesh_terms: D000110:Acetylcholinesterase / Q000378:metabolism*; D002800:Cholinesterase Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D006801:Humans; D062105:Molecular Docking Simulation; D015394:Molecular Structure; D012603:Scopoletin / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship
chemical_list: D002800:Cholinesterase Inhibitors; D000110:Acetylcholinesterase; D012603:Scopoletin
keywords: Acetylcholinesterase inhibitor; Pyridinium derivatives; Scopoletin; Synthesis