title: Synthesis and evaluation of 4-substituted coumarins as novel acetylcholinesterase inhibitors.
abstract: A series of 4-hydroxycoumarin derivatives were designed and synthesized as new acetylcholinesterase (AChE) inhibitors which could be considered for Alzheimer's disease therapeutics. Among the 19 coumarin-derived compounds tested toward Electrophorus electricus acetylcholinesterase (eelAChE) and horse serum butyrylcholinesterase (eqBChE), N-(1-benzylpiperidin-4-yl)acetamide derivative 4m displayed highest AChE inhibitory activity (IC50 = 1.2 μM) and good selectivity (37 times). The docking study of the most potent compound 4m, indicated that Phe330 is responsible for ligand recognition and trafficking by forming π-cation interaction with benzylpiperidine moiety. Furthermore, the formation of an additional π-π interaction between coumarin moiety and Trp279 of peripheral anionic site could stabilize the ligand in the active site resulting in more potent inhibition of the enzyme.
authors: Department of Chemistry, University of Zanjan, P.O. Box 45195-313, Zanjan, Iran.
authors: Seyyede Faeze
authors: SF
authors: Razavi
authors: Mehdi
authors: M
authors: Khoobi
authors: Hamid
authors: H
authors: Nadri
authors: Amirhossein
authors: A
authors: Sakhteman
authors: Alireza
authors: A
authors: Moradi
authors: Saeed
authors: S
authors: Emami
authors: Alireza
authors: A
authors: Foroumadi
authors: Abbas
authors: A
authors: Shafiee
mesh_terms: D000110:Acetylcholinesterase / Q000378:metabolism*; D000818:Animals; D002091:Butyrylcholinesterase / Q000378:metabolism*; D002800:Cholinesterase Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D003374:Coumarins / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004593:Electrophorus; D006736:Horses; D008958:Models, Molecular; D015394:Molecular Structure; D013329:Structure-Activity Relationship
chemical_list: D002800:Cholinesterase Inhibitors; D003374:Coumarins; D000110:Acetylcholinesterase; D002091:Butyrylcholinesterase