新型芳香族多胺共轭物作为胆碱酯酶抑制剂，对丁酰胆碱酯酶具有显著的选择性。
Novel aromatic-polyamine conjugates as cholinesterase inhibitors with notable selectivity toward butyrylcholinesterase.
作者信息
Hong Chen, Luo Wen, Yao Dong, Su Ya-Bin, Zhang Xin, Tian Run-Guo, Wang Chao-Jie
机构信息
Key Laboratory of Natural Medicine and Immuno-Engineering, Henan University, Kaifeng 475004, People's Republic of China.
Key Laboratory of Natural Medicine and Immuno-Engineering, Henan University, Kaifeng 475004, People's Republic of China.
出版信息
Bioorg Med Chem. 2014 Jun 15;22(12):3213-9. doi: 10.1016/j.bmc.2014.03.045. Epub 2014 Apr 13.
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.
设计、合成并评估了三种类型的芳香族多胺缀合物（6a - 6s）作为胆碱酯酶（ChEs）的潜在抑制剂。结果表明，蒽醌 - 多胺缀合物（AQPCs）表现出最有效的乙酰胆碱酯酶（AChE）抑制活性，IC50值为1.50至11.13 μM。蒽 - 多胺缀合物（APCs）显示出惊人的选择性（76至3125倍），并且在抑制丁酰胆碱酯酶（BChE）方面最有效，IC50值为0.016至0.657 μM。Lineweaver - Burk图和分子模拟研究表明，代表性化合物6l和6k靶向ChEs的催化活性位点（CAS）和外周阴离子位点（PAS）。此外，APCs在100 μM浓度下不影响HepG2细胞活力。因此，这些多胺缀合物可用于治疗阿尔茨海默病（AD）的全面而系统的研究。
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