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http://dx.doi.org/10.5012/bkcs.2013.34.4.1025

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

Yeun, Go Heum (Department of Chemical & Biological Engineering, Hanbat National University)
Lee, Seung Hwan (Department of Chemical & Biological Engineering, Hanbat National University)
Lim, Yong Bae (Department of Chemical & Biological Engineering, Hanbat National University)
Lee, Hye Sook (Department of Chemical & Biological Engineering, Hanbat National University)
Won, Moo-Ho (Department of Neurobiology, School of Medicine, Kangwon National University)
Lee, Bong Ho (Department of Chemical & Biological Engineering, Hanbat National University)
Park, Jeong Ho (Department of Chemical & Biological Engineering, Hanbat National University)
Publication Information
Bulletin of the Korean Chemical Society / v.34, no.4, 2013 , pp. 1025-1029 More about this Journal
Abstract
In the previous paper (Bull. Korean Chem. Soc., 2011, 32, 2997), the hybrid molecules between ${\alpha}$-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 $IC_{50}$ 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 ($IC_{50}=0.44{\pm}0.24{\mu}M$). 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 $4.3{\pm}0.09{\mu}M$.
Keywords
Molecular hybridization; ${\alpha}$-Lipoic acid (ALA); Polyphenols(PPs); Butyrylcholinesterase inhibitor; 2-(Piperazin-1-yl)ethanol linker;
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