Design, synthesis and cholinesterase inhibitory activity of quinoline-polyamine conjugates.
- Author:
Wen LUO
1
;
Kai HUANG
;
Zhen ZHANG
;
Chen HONG
;
Chao-Jie WANG
Author Information
1. Key Laboratory of Natural Medicine and Immuno-Engineering, Henan University, Kaifeng 475004, China. luowen83@henu.edu.cn
- Publication Type:Journal Article
- MeSH:
Acetylcholinesterase;
metabolism;
Butyrylcholinesterase;
metabolism;
Cholinesterase Inhibitors;
chemical synthesis;
chemistry;
pharmacology;
Drug Design;
Inhibitory Concentration 50;
Polyamines;
chemical synthesis;
chemistry;
pharmacology;
Quinolines;
chemical synthesis;
chemistry;
pharmacology;
Structure-Activity Relationship
- From:
Acta Pharmaceutica Sinica
2013;48(2):269-275
- CountryChina
- Language:Chinese
-
Abstract:
A series of quinoline-polyamine conjugates (8a-8n) were designed, synthesized and evaluated as inhibitors of cholinesterases (ChEs). Some of these compounds had potent ChEs inhibitory activity with IC50 values at micromolar range. Compound 8n exhibited the strongest inhibition on acetylcholinesterase (AChE) with an IC50 value of 8.78 micromol x L(-1), and compound 8i showed the most potent inhibition on butyrylcholinesterase (BChE) with IC50 value of 1.60 micromol x L(-1) which was slightly better than rivastigmine. The structure-activity relationship revealed that the chain length of polyamine and linker played important roles for inhibitory activity. Molecular modeling studies showed that 8i targeted both the catalytic active site (CAS) and the peripheral anionic site (PAS) of cholinesterases.
