Design, synthesis and evaluation of flavonoid derivatives as potent AChE inhibitors.
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.
Sheng
Rong
R
ZJU-ENS Joint Laboratory of Medicinal Chemistry, School of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, PR China.
Lin
Xiao
X
Zhang
Jing
J
Chol
Kim Sun
KS
Huang
Wenhai
W
Yang
Bo
B
He
Qiaojun
Q
Hu
Yongzhou
Y
D000110:Acetylcholinesterase / Q000737:chemistry / Q000378:metabolism*; D000818:Animals; D001665:Binding Sites; D002091:Butyrylcholinesterase / Q000737:chemistry / Q000378:metabolism; D002800:Cholinesterase Inhibitors / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D003198:Computer Simulation; D005419:Flavonoids / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D020128:Inhibitory Concentration 50; D008958:Models, Molecular; D015394:Molecular Structure; D048448:Phenylcarbamates / Q000494:pharmacology; D011485:Protein Binding; D051381:Rats; D000068836:Rivastigmine; D013329:Structure-Activity Relationship
D002800:Cholinesterase Inhibitors; D005419:Flavonoids; D048448:Phenylcarbamates; D000110:Acetylcholinesterase; D002091:Butyrylcholinesterase; D000068836:Rivastigmine