Design, synthesis and evaluation of difunctionalized 4-hydroxybenzaldehyde derivatives as novel cholinesterase inhibitors.
A series of difunctionalized 4-hydroxybenzaldehyde derivatives were designed, synthesized and evaluated as cholinesterase (acetylcholinesterase (AChE) and butyrylcholinesterase (BChE)) inhibitors. The results demonstrated that all the compounds had more potent AChE and BChE inhibitory activities than galanthamine-HBr, one of the best cholinesterase inhibitors known so far. The inhibition mechanism revealed that the best active compound 4e displayed a mix-type mode of AChE and BChE by its dual-site interactions with the catalytic triad active center and the peripheral anionic site (PAS) of enzyme. All these data suggested that further development of such compounds may be of interest.
Yu
Liang
L
School of Chemistry and Chemical Engineering, Sun Yat-sen University, Guangzhou 510275, China.
Cao
Rihui
R
Yi
Wei
W
Yan
Qin
Q
Chen
Zhiyong
Z
Ma
Lin
L
Song
Huacan
H
D000110:Acetylcholinesterase / Q000378:metabolism*; D000818:Animals; D001547:Benzaldehydes / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D002091:Butyrylcholinesterase / Q000378:metabolism*; D002800:Cholinesterase Inhibitors / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D004593:Electrophorus; D006736:Horses; D015394:Molecular Structure
D001547:Benzaldehydes; D002800:Cholinesterase Inhibitors; D000110:Acetylcholinesterase; D002091:Butyrylcholinesterase; C011483:4-hydroxybenzaldehyde