喹啉-多胺缀合物的设计、合成及胆碱酯酶抑制活性
[Design, synthesis and cholinesterase inhibitory activity of quinoline-polyamine conjugates].
作者信息
Luo Wen, Huang Kai, Zhang Zhen, Hong Chen, Wang Chao-Jie
机构信息
Key Laboratory of Natural Medicine and Immuno-Engineering, Henan University, Kaifeng 475004, China.
出版信息
Yao Xue Xue Bao. 2013 Feb;48(2):269-75.
A series of quinoline-polyamine conjugates (8a-8n) were designed, synthesized and evaluated as inhibitors of cholinesterases (ChEs). Some of these compounds had potent ChEs inhibitory activity with IC50 values at micromolar range. Compound 8n exhibited the strongest inhibition on acetylcholinesterase (AChE) with an IC50 value of 8.78 micromol x L(-1), and compound 8i showed the most potent inhibition on butyrylcholinesterase (BChE) with IC50 value of 1.60 micromol x L(-1) which was slightly better than rivastigmine. The structure-activity relationship revealed that the chain length of polyamine and linker played important roles for inhibitory activity. Molecular modeling studies showed that 8i targeted both the catalytic active site (CAS) and the peripheral anionic site (PAS) of cholinesterases.
设计、合成了一系列喹啉 - 多胺缀合物（8a - 8n），并将其作为胆碱酯酶（ChEs）抑制剂进行评估。其中一些化合物具有较强的胆碱酯酶抑制活性，IC50值在微摩尔范围内。化合物8n对乙酰胆碱酯酶（AChE）表现出最强的抑制作用，IC50值为8.78 μmol·L⁻¹，化合物8i对丁酰胆碱酯酶（BChE）表现出最有效的抑制作用，IC50值为1.60 μmol·L⁻¹，略优于利伐斯的明。构效关系表明，多胺链长度和连接基对抑制活性起重要作用。分子模拟研究表明，8i靶向胆碱酯酶的催化活性位点（CAS）和外周阴离子位点（PAS）。
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