Development of Cholinesterase Inhibitors using 1-Benzyl Piperidin-4-yl (α)-Lipoic Amide Molecules

Bulletin of the Korean chemical society

Beom-cheol Kim¹  Hye Sook Lee¹  Min Young Shon¹  Jae-kwan Kim¹  Seung-hwan Lee¹  Jeong Ho Park¹ 

关键词: Molecular hybridization;    ()-Lipoic acid;    4-Amino-1-benzyl piperidines;    Cholinesterase inhibitors;   

DOI  :  

学科分类：化学（综合）

来源: Korean Chemical Society

【 摘 要 】

A series of hybrid molecules between (α)-lipoic acid (ALA) and 4-amino-1-benzyl piperidines were synthesized and their in vitro cholinesterase (acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE)) inhibitory activities were evaluated. Even though the parent compounds did not exhibit any inhibitory activity against cholinesterase (ChE) with the exception of compound 14 (IC50 = 255.26 ± 4.41 against BuChE), all hybrid molecules demonstrated BuChE inhibitory activity. Some hybrid compounds also displayed AChE inhibitory activity. Specifically, compound 17 was shown to be an effective inhibitor against both AChE (IC50 = 1.75 ± 0.30 μM) and BuChE (IC50 = 5.61 ± 1.25 μM) comparable to galantamine (IC50 = 1.7 ± 0.9 μM against AChE and IC50 = 9.4 ± 2.5 μM against BuChE). Inhibition kinetic studies using compound 17 indicated a mixed inhibition type for AChE and a noncompetitive inhibition type for BuChE. Its binding affinity (Ki) values to AChE and BuChE were 3.8 ± 0.005 μM and 7.0 ± 0.04 μM, respectively.

【 授权许可】

Unknown