(2013) Synthesis and evaluation of 4-substituted coumarins as novel acetylcholinesterase inhibitors. European Journal of Medicinal Chemistry. pp. 252-259.
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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 �-cation interaction with benzylpiperidine moiety. Furthermore, the formation of an additional �-� 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. © 2013 Elsevier Masson SAS. All rights reserved.
| Item Type: | Article |
|---|---|
| Keywords: | 2 (2 oxo 2h chromen 4 yloxy)acetic acid; 4 (2 oxo 2h chromen 4 yloxy)butanoic acid; 4 2 (4 benzylpiperidin 1 yl) 2 oxoethoxy) 2h chromen 2 one; 4 2 4 (2 fluorophenyl)piperazin 1 yl 2 oxoethoxy) 2h chromen 2 one; 4 2 4 (2 hydroxyphenyl)piperazin 1 yl] 2 oxoethoxy] 2h chromen 2 one; 4 2 4 (3,4 dichlorophenyl)piperazin 1 yl] 2 oxoethoxy 2h chromen 2 one; 4 2 4 (4 bromophenyl) 4 hydroxypiperidin 1 yl] 2 oxoethoxy] 2h chromen 2 one; 4 2 4 (4 chlorophenyl) 4 hydroxypiperidin 1 yl] 2 oxoethoxy] 2h chromen 2 one; 4 2 4 (4 fluorophenyl)piperazin 1 yl] 2 oxoethoxy] 2h chromen 2 one; 4 2 oxo 2 (4 phenylpiperazin 1 yl)ethoxy) 2h chromen 2 one; 4 4 (4 benzylpiperidin 1 yl) 4 oxobutoxy 2h chromen 2 one; 4 4 4 (2 fluorophenyl)piperazin 1 yl] 4 oxobutoxy] 2h chromen 2 one; 4 4 4 (2 hydroxyphenyl)piperazin 1 yl] 4 oxobutoxy] 2h chromen 2 one; 4 4 4 (3,4 dichlorophenyl)piperazin 1 yl] 4 oxobutoxy] 2h chromen 2 one; 4 4 4 (4 bromophenyl) 4 hydroxypiperidin 1 yl] 4 oxobutoxy] 2h chromen 2 one; 4 4 4 (4 chlorophenyl) 4 hydroxypiperidin 1 yl] 4 oxobutoxy] 2h chromen 2 one; 4 4 4 (4 fluorophenyl)piperazin 1 yl] 4 oxobutoxy] 2h chromen 2 one; 4 4 oxo 4 (4 phenylpiperazin 1 yl)butoxy 2h chromen 2 one; acetylcholinesterase; ap 2238; cholinesterase; cholinesterase inhibitor; coumarin derivative; ensaculine; enzyme inhibitor; n(1 benzylpiperidin 4 yl) 2 (2 oxo 2h chromen 4 yloxy)acetamide; n(1 benzylpiperidin 4 yl) 4 (2 oxo 2h chromen 4 yloxy)butanamide; n(3,4 dimethoxyphenethyl) 4 (2 oxo 2h chromen 4 yloxy)butanamide; unclassified drug, antioxidant activity; article; drug design; drug selectivity; drug synthesis; Electrophorus; enzyme inhibition; evaluation; horse; IC 50; molecular docking; molecular recognition; nonhuman; substitution reaction, Acetylcholinesterase; Animals; Butyrylcholinesterase; Cholinesterase Inhibitors; Coumarins; Dose-Response Relationship, Drug; Electrophorus; Horses; Models, Molecular; Molecular Structure; Structure-Activity Relationship |
| Page Range: | pp. 252-259 |
| Journal or Publication Title: | European Journal of Medicinal Chemistry |
| Volume: | 64 |
| Depositing User: | ms soheila Bazm |
| URI: | http://eprints.ssu.ac.ir/id/eprint/8825 |
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