Synthesis and biological evaluation of helicid analogues as novel acetylcholinesterase inhibitors

Huan Wen; Chonglan Lin; Ling Que; Hui Ge; Lin Ma; Rihui Cao; Yiqian Wan; Wenlie Peng; Zihou Wang; Huacan Song

doi:10.1016/j.ejmech.2007.03.018

Synthesis and biological evaluation of helicid analogues as novel acetylcholinesterase inhibitors

Eur J Med Chem. 2008 Jan;43(1):166-73. doi: 10.1016/j.ejmech.2007.03.018. Epub 2007 Apr 5.

Authors

Huan Wen¹, Chonglan Lin, Ling Que, Hui Ge, Lin Ma, Rihui Cao, Yiqian Wan, Wenlie Peng, Zihou Wang, Huacan Song

Affiliation

¹ School of Chemistry and Chemical Engineering, Sun Yat-sen University, Guangzhou 510275, China.

PMID: 17574306
DOI: 10.1016/j.ejmech.2007.03.018

Abstract

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Acetylcholinesterase / metabolism*
Benzaldehydes / chemical synthesis*
Benzaldehydes / chemistry
Benzaldehydes / metabolism
Benzaldehydes / pharmacology*
Biological Products / chemistry
Biological Products / metabolism
Biological Products / pharmacology
Cholinesterase Inhibitors / chemical synthesis*
Cholinesterase Inhibitors / chemistry
Cholinesterase Inhibitors / metabolism
Cholinesterase Inhibitors / pharmacology
Drug Evaluation, Preclinical
Glycosides / pharmacology
Humans
Inhibitory Concentration 50
Kinetics
Schiff Bases / chemistry
Sensitivity and Specificity
Spectrophotometry, Ultraviolet

Substances

Benzaldehydes
Biological Products
Cholinesterase Inhibitors
Glycosides
Schiff Bases
helicide
Acetylcholinesterase