Development of Cholinesterase Inhibitors Using (a)-Lipoic Acid-benzyl Piperazine Hybrid Molecules

Bulletin of the Korean chemical society

Beom-cheol Kim¹  Mi Jang¹  MinYoung Shon¹  Seung-hwan Lee¹  Jeong Ho Park¹ 

关键词: Molecular hybridization;    ()-Lipoic acid;    Benzyl piperazines;    Butyrylcholinesterase inhibitor;   

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 benzyl piperazines were synthesized and their in vitro cholinesterase [acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE)] inhibitory activities were evaluated. Even though the parent compounds did not show any inhibitory activity against cholinesterase (ChE), all hybrid molecules showed BuChE inhibitory activity. Some hybrid compounds also displayed AChE inhibitory activity. Specifically, ALA-1-(3-methylbenzyl)piperazine (15) was shown to be an effective inhibitor of both BuChE (IC50 = 2.3 ± 0.7 μM) and AChE (IC50 = 30.31 ± 0.64 μM). An inhibition kinetic study using compound 15 indicated a mixed inhibition type. Its binding affinity (Ki) value to BuChE is 2.91 ± 0.15 μM.

【 授权许可】

Unknown