Synthesis, docking study, and biological evaluation of novel umbellipherone/hymecromone derivatives as acetylcholinesterase/butyrylcholinesterase inhibitors

A novel hybrid series of umbellipherone and benzyl amine scaffolds, linked via triazole ring, was synthesized and evaluated as both acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) inhibitors. Most of the synthesized compounds showed moderate to high activities by using Ellman’s modified assay. Among the target compounds, 6e bearing 3-methoxy substituent on benzyl moiety was the most active one (AChE and BuChE IC 50 = 3.4 and 1.1 μM, respectively). Finally, binding modes of the target compound was studied using molecular docking stimulations. The neuroprotectivity evaluation exhibited that this compound efficiently protected PC12 neurons against H 2 O 2 -induced cell death.