Cholinesterase Inhibitory Activity, Kinetic and Molecular Docking Studies of N-(1-substituted-1H-1,2,3-triazole-4-yl)-aralkylamide Derivatives

Woralak PETRAT, Chatchai WATTANAPIROMSAKUL, Teerapat NUALNOI, Nadia Hanim SABRI, Vannajan Sanghiran LEE LEE, Luelak LOMLIM


Acetylcholinesterase (AChE) inhibitors are widely used for treatment of Alzheimer’s disease (AD). With the ultimate goal of improving the efficiency of AChE inhibitors currently used in AD treatment, in this study, a total number of 14 compounds of N-(1-substituted-1H-1,2,3-triazole-4-yl)-aralkylamide derivatives were designed, synthesized, and investigated for their AChE and butyrylcholinesterase (BuChE) inhibitory activities. The most potent AChE inhibitor in this series was 6e (IC50 15.01 mM against human AChE). The inhibition kinetics of 6e indicated that the compound was a noncompetitive inhibitor of acetylcholinesterase. A molecular docking study supported the idea that the aromatic moieties of 6e interacted with both a catalytic anionic site and a peripheral anionic site of acetylcholinesterase, while the 1,2,3-triazole ring also formed van der Waals and hydrogen bond interactions with the amino acid residues in the mid-gorge of the enzyme.


1,2,3-triazole, acetylcholinesterase inhibitor, butyrylcholinesterase inhibitor, enzyme kinetic study, molecular docking

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