Design, synthesis and evaluation of bis-nicotine derivatives as inhibitors of cholinesterases and beta-amyloid aggregation.
- Author:
Wen LUO
1
;
Yong-mei ZHAO
2
;
Run-guo TIAN
3
;
Ya-bin SU
3
;
Chen HONG
3
Author Information
1. Key Laboratory of Natural Medicine and Immuno-Engineering, Henan University, Kaifeng 475004, China. luowen83@henu.edu.cn
2. Pharmaceutical School of Henan Province, Kaifeng 475001, China.
3. Key Laboratory of Natural Medicine and Immuno-Engineering, Henan University, Kaifeng 475004, China.
- Publication Type:Journal Article
- MeSH:
Acetylcholinesterase;
metabolism;
Amyloid beta-Peptides;
antagonists & inhibitors;
metabolism;
Binding Sites;
Butyrylcholinesterase;
metabolism;
Cholinesterase Inhibitors;
chemical synthesis;
chemistry;
pharmacology;
Nicotine;
analogs & derivatives;
chemical synthesis;
chemistry;
pharmacology
- From:
Acta Pharmaceutica Sinica
2013;48(11):1671-1676
- CountryChina
- Language:Chinese
-
Abstract:
A novel series of bis-nicotine derivatives (3a-3i) were designed, synthesized and evaluated as bivalent anti-Alzheimer's disease agents. The pharmacological results indicated that compounds 3e-3i inhibited both acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) in the micromolar range (IC50, 2.28-117.86 micromol x L(-1) for AChE and 1.67-125 micromol x L(-1) for BChE), which was at the same potency as rivastigmine. A Lineweaver-Burk plot and molecular modeling study showed that these derivatives targeted both the catalytic active site (CAS) and the peripheral anionic site (PAS) of AChE. Besides, these compounds could significantly inhibit the self-induced Abeta aggregation with inhibition activity (11.85%-62.14%) at the concentration of 20 micromol x L(-1).
