Synthesis of Selective Butyrylcholinesterase Inhibitors Coupled between α-Lipoic Acid and Polyphenols by Using 2-(Piperazin-1-yl)ethanol Linker

Bulletin of the Korean chemical society

Go Heum Yeun¹  Bong Ho Lee¹  Hye Sook Lee¹  Moo-Ho Won¹  Seung Hwan Lee¹  Yong Bae Lim¹  Jeong Ho Park¹ 

关键词: Molecular hybridization;    -Lipoic acid (ALA);    Polyphenols (PPs);    Butyrylcholinesterase inhibitor;    2-(Piperazin-1-yl)ethanol linker;   

DOI  :  

学科分类：化学（综合）

来源: Korean Chemical Society

【 摘 要 】

In the previous paper (Bull. Korean Chem. Soc., 2011, 32, 2997), the hybrid molecules between α-lipoic acid (ALA) and polyphenols (PPs) connected with neutral 2-(2-aminoethoxy)ethanol linker (linker-1) showed new biological activity such as butyrylcholinesterase (BuChE) inhibition. In order to increase the binding affinity of the hybrid compounds to cholinesterase (ChE), the neutral 2-(2-aminoethoxy)ethanol (linker 1) was switched to the cationic 2-(piperazin-1-yl)ethanol linker (linker 2). The IC50 values of the linker-2 hybrid molecules for BuChE inhibition were lower than those of linker-1 hybrid molecules (except 9-2) and they also had the same great selectivity for BuChE over AChE (> 800 fold) as linker-1 hybrid molecules. ALA-acetyl caffeic acid (10- 2, ALA-AcCA) was shown as an effective inhibitor of BuChE (IC50 = 0.44 ± 0.24 μM). A kinetic study using 7- 2 showed that it is the same mixed type inhibition as 7-1. Its inhibition constant (Ki) to BuChE is 4.3 ± 0.09 μM.

【 授权许可】

Unknown