他克林-苯酚-联苯双酯杂合...碱酯酶抑制活性及肝毒性评价 洪琛.pdf

: .
药学学报
0 值为 nmol·L ，
-1
7b 对丁酰胆碱酯酶的活性最强，IC50 值为 nmol·L 。酶动力学及分子对接表明化
合物 8d 能够同时作用于 AChE 的催化活性位点和外周结合位点。另外，这些化合物对
肝细胞的体外毒性较低，8d 没有明显增加 HepG2 细胞内活性氧水平。
关键词：他克林；胆碱酯酶；肝毒性；阿尔茨海默症
中图分类号：R914 文献标志码：A

Synthesis, cholinesterase inhibition and hepatotoxicity of
tacrine-phenol-bifendate hybrids
HONG Chen 1, ZHAO Yong-mei 2*, GUO Hui-yan 3, LUO Wen 3*
(1. Huaihe Hospital, Henan University, Kaifeng 475004, China; 2. Pharmaceutical
Engineering Department, Henan Vocational College of Applied Technology, Kaifeng 475004,

收稿日期：2022-04-18；修回日期：2022-05-13.
基金项目:河南省医学科技攻关计划项目(2018020333); 河南省重点研发与推广专项
(2**********);河南应用技术职业学院项目(2020-HJ-22).
*通讯作者 Tel: **********, E-mail: zhaoyongmei_******@; Tel: **********, E-mail:
******@

China; 3. Key Laboratory of Natural Medicine and Immuno-Engineering, Henan University,
Kaifeng 475004, China)
Abstract: A series of tacrine-phenol-bifendate hybrids (7a-7e, 8a-8e) were designed,
synthesized and evaluated as inhibitors of cholinesterases (ChEs) with low hepatotoxicity. All
the compounds had potent ChEs inhibitory activity with half-inhibitory concentration (IC50)
values at the nanomolar range. Compound 8d exhibited the strongest inhibition to
-1
acetylcholinesterase (AChE) with an IC50 value of nmol·L and compound 7b showed