Design, synthesis and evaluation of genistein-polyamine conjugates as multi-functional anti-Alzheimer agents

作     者：Xin Zhang Jiang Wang Chen Hong Wen Luo Chaojie Wang 

作者机构：Key Laboratory of Natural Medicine and Immuno-Engineering Henan University 

出 版 物：《Acta Pharmaceutica Sinica B》 (药学学报（英文版）)

年 卷 期：2015年第5卷第1期

页      面：67-73页

核心收录：

学科分类：1007[医学-药学(可授医学、理学学位)] 1004[医学-公共卫生与预防医学(可授医学、理学学位)] 1001[医学-基础医学(可授医学、理学学位)] 100701[医学-药物化学] 10[医学] 

基　　金：the National Natural Science Foundation of China (Nos. 21172053 and 21302041) the China Postdoctoral Science Foundation (No. 2012M521391) the Postdoctoral Science Foundation of Henan Province (No. 2011015) the Foundation of Henan Educational Committee (No. 14A350008) 

主　　题：Genistein Polyamine Alzheimer’s disease Acetylcholinesterase Molecular modeling Metal-chelating Inhibition Rivastigmine 

摘      要：A series of genistein-polyamine conjugates(4a–4h) were designed, synthesized and evaluated as multi-functional anti-Alzheimer agents. The results showed that these compounds had significant cholinesterases(Ch Es) inhibitory activity. Compound 4b exhibited the strongest inhibition to acetylcholinesterase(ACh E) with an IC_(50) value of 2.75 μmol/L, which was better than that of rivastigmine(5.60 μmol/L). Lineweaver–Burk plot and molecular modeling study showed that compound 4b targeted both the catalytic active site(CAS) and the peripheral anionic site(PAS) of ACh E. Besides, compound 4b showed potent metal-chelating ability. In addition, it was found that 4a–4h did not affect Hep G-2 cell viability at the concentration of 10 μmol/L.