Design, synthesis and evaluation of flavonoid derivatives as potent AChE inhibitors

Abstract

A new series of flavonoid derivatives have been designed, synthesized and evaluated as potent AChE inhibitors. Most of them showed more potent inhibitory activities to AChE than rivastigmine. The most potent inhibitor isoflavone derivative 10d inhibit AChE with a IC 50 of 4 nM and showed high BChE/AChE inhibition ratio (4575-fold), superior to donepezil (IC 50 = 12 nM, 389-fold). Molecular docking studies were also performed to explore the detailed interaction with AChE.