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本文设计合成了系列喹啉多胺缀合物(8a～8n)并对其进行了胆碱酯酶抑制活性测试。结果表明部分化合物IC50值达到微摩尔级,其中化合物8n对乙酰胆碱酯酶(acetylcholinesterase,AChE)的抑制活性最强,IC50值为8.78μmol.L 1,8i对丁酰胆碱酯酶(butyrylcholinesterase,BChE)的活性最强,IC50值为1.60μmol.L 1,略优于对照药物rivastigmine。构效关系研究表明,多胺链的长度和连接基团对活性影响较大。分子对接表明化合物8i作用在AChE的催化活性位点(catalytic active site,CAS)和外周阴离子位点(peripheral anionic site,PAS)。
In this paper, a series of quinoline polyamine conjugates (8a ~ 8n) were synthesized and tested for their cholinesterase inhibitory activity. The results showed that the IC50 values of some compounds reached micromolar. Among them, compound 8n showed the strongest inhibitory activity against acetylcholinesterase (AChE) with an IC50 value of 8.78μmol.L 1,8i inhibited butyrylcholinesterase (BChE) ) Had the strongest activity with an IC50 value of 1.60 μmol·L -1, slightly better than the control drug rivastigmine. The structure-activity relationship studies show that the length of the polyamine chain and the linker have a great effect on the activity. Molecular docking showed that compound 8i acted on the catalytic active site (AChE) and peripheral anionic site (PAS) of AChE.