Twelve novel 7-diethylaminocoumarin-based 1,3,4-oxadiazole derivatives were synthesized via iodine-mediated oxidative cyclisation and confirmed by 1H NMR, 13C NMR and HRMS. The result of these derivatives' activities inhibiting acetylcholinesterase in vitro showed that 4 g and 4i had moderate inhibitory activities with 69.19% and 65.06%, respectively. The preliminary structure-activity relationships revealed that introduction of halogen atom on the para-position of phenyl of 7-diethylaminocoumarin-based 1,3,4-oxadiazole derivatives could enhance their activities. Molecular docking study suggested that 4 g possessed an optimal docking pose with interactions inside AChE.
Keywords: 1,3,4-oxadiazole; Coumarin; acetylcholinesterase inhibitor; molecular docking.