2. Academic Validation
  3. Novel aromatic-polyamine conjugates as cholinesterase inhibitors with notable selectivity toward butyrylcholinesterase

Novel aromatic-polyamine conjugates as cholinesterase inhibitors with notable selectivity toward butyrylcholinesterase

  • Bioorg Med Chem. 2014 Jun 15;22(12):3213-9. doi: 10.1016/j.bmc.2014.03.045.
Chen Hong 1,  Wen Luo 2,  Dong Yao 1,  Ya-Bin Su 1,  Xin Zhang 1,  Run-Guo Tian 1,  Chao-Jie Wang 3
Affiliations

Affiliations

  • 1 Key Laboratory of Natural Medicine and Immuno-Engineering, Henan University, Kaifeng 475004, People's Republic of China.
  • 2 Key Laboratory of Natural Medicine and Immuno-Engineering, Henan University, Kaifeng 475004, People's Republic of China. Electronic address: luowen83@henu.edu.cn.
  • 3 Key Laboratory of Natural Medicine and Immuno-Engineering, Henan University, Kaifeng 475004, People's Republic of China. Electronic address: wcjsxq@henu.edu.cn.
PMID: 24794747 DOI: 10.1016/j.bmc.2014.03.045
Abstract

Three types of aromatic-polyamine conjugates (6a-6s) were designed, synthesized and evaluated as potential inhibitors for cholinesterases (ChEs). The results showed that anthraquinone-polyamine conjugates (AQPCs) exhibited the most potent acetylcholinesterase (AChE) inhibitory activity with IC50 values from 1.50 to 11.13 μM. Anthracene-polyamine conjugates (APCs) showed a surprising selectivity (from 76- to 3125-fold) and were most potent at inhibiting butyrylcholinesterase (BChE), with IC50 values from 0.016 to 0.657 μM. A Lineweaver-Burk plot and molecular modeling studies indicated that the representative compounds, 6l and 6k, targeted both the catalytic active site (CAS) and the peripheral anionic site (PAS) of ChEs. Furthermore, APCs did not affect HepG2 cell viability at the concentration of 100 μM. Consequently, these polyamine conjugates could be thoroughly and systematically studied for the treatment of AD.

Keywords

Acetylcholinesterase; Alzheimer’s disease; Butyrylcholinesterase; Polyamine conjugates.

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