Synthesis and biological evaluation of helicid analogues as novel acetylcholinesterase inhibitors.
A series of helicid analogues were prepared and evaluated in vitro for the cholinesterase (AChE and BuChE) inhibitory activities via UV spectroscopy. The results indicated that compounds 5, 6d and 8 exhibited potent AChE inhibitory activities with IC(50) values of 0.45+/-0.02microM, 0.49+/-0.02microM, and 0.20+/-0.01microM, respectively. High selectivity for AChE over BuChE was also observed. Kinetic study showed that the mechanism of AChE inhibition of compounds 5, 6d and 8 was all mixed-type.
Wen
Huan
H
School of Chemistry and Chemical Engineering, Sun Yat-sen University, Guangzhou 510275, China.
Lin
Chonglan
C
Que
Ling
L
Ge
Hui
H
Ma
Lin
L
Cao
Rihui
R
Wan
Yiqian
Y
Peng
Wenlie
W
Wang
Zihou
Z
Song
Huacan
H
D000110:Acetylcholinesterase / Q000378:metabolism*; D001547:Benzaldehydes / Q000138:chemical synthesis* / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D001688:Biological Products / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D002800:Cholinesterase Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D004353:Drug Evaluation, Preclinical; D006027:Glycosides / Q000494:pharmacology; D006801:Humans; D020128:Inhibitory Concentration 50; D007700:Kinetics; D012545:Schiff Bases / Q000737:chemistry; D012680:Sensitivity and Specificity; D013056:Spectrophotometry, Ultraviolet
D001547:Benzaldehydes; D001688:Biological Products; D002800:Cholinesterase Inhibitors; D006027:Glycosides; D012545:Schiff Bases; C055677:helicide; D000110:Acetylcholinesterase