Design and synthesis of 7-diethylaminocoumarin-based 1,3,4-oxadiazole derivatives with anti-acetylcholinesterase activities

Abstract

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.

Graphical abstract

Keywords:

• Coumarin
• 1,3,4-oxadiazole
• acetylcholinesterase inhibitor
• molecular docking

Disclosure statement

No potential conflict of interest was reported by the authors.

Additional information

Funding

This work was supported by the Science and Technology Fund of Guizhou [QKH-PTRC(2017)5735-22], Guizhou Provincial Natural Science Foundation [QKH-J(2020)1Y070] and the Youth Talent Development Project of Guizhou Provincial Department of Education [2017]169.