Bulletin of the Korean Chemical Society

Korean Chemical Society (대한화학회)
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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)
  • Received : 2012.12.17
  • Accepted : 2013.01.03
  • Published : 2013.04.20
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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 $4.3{\pm}0.09{\mu}M$.

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References

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