Wu Gaochan, Gao Yun, Kang Dongwei, Huang Boshi, Huo Zhipeng, Liu Huiqing, Poongavanam Vasanthanathan, Zhan Peng, Liu Xinyong
Department of Medicinal Chemistry , Key Laboratory of Chemical Biology (Ministry of Education) , School of Pharmaceutical Sciences , Shandong University , 44 West Culture Road , 250012 Jinan , Shandong , PR China . Email:
Institute of Pharmacology , School of Medicine , Shandong University , 44 West Culture Road , 250012 Jinan , Shandong , PR China.
Medchemcomm. 2017 Dec 1;9(1):149-159. doi: 10.1039/c7md00457e. eCollection 2018 Jan 1.
We report herein the design and synthesis of a series of 11 novel tacrine-1,2,3-triazole derivatives a Cu(i)-catalyzed alkyne-azide 1,3-dipolar cycloaddition (CuAAC) reaction. The newly synthesized compounds were evaluated for their inhibition activity against acetylcholinesterase (AChE) and horse serum butyrylcholinesterase (BChE) as potential drug targets for Alzheimer's disease (AD). Among the designed compounds, compound exhibited potent inhibition against AChE and BChE with IC values of 4.89 μM and 3.61 μM, respectively. Further structure-activity relationship (SAR) and molecular modeling studies may provide valuable insights into the design of better tacrine-triazole analogues with potential therapeutic applications for AD.
我们在此报告了一系列11种新型他克林-1,2,3-三唑衍生物的设计与合成，该反应通过铜（I）催化的炔烃-叠氮化物1,3-偶极环加成（CuAAC）反应实现。对新合成的化合物针对乙酰胆碱酯酶（AChE）和马血清丁酰胆碱酯酶（BChE）的抑制活性进行了评估，它们是阿尔茨海默病（AD）潜在的药物靶点。在设计的化合物中，化合物对AChE和BChE表现出强效抑制作用，IC值分别为4.89 μM和3.61 μM。进一步的构效关系（SAR）和分子模拟研究可能为设计具有AD潜在治疗应用的更好的他克林-三唑类似物提供有价值的见解。
