染料木素氨基甲酸酯类衍生物的合成及生物活性研究  

Synthesis and Biological Evaluation of Genistein Carbamate Derivatives

作　　者：强晓明[1] 袁文[1] 桑志培[1] 邓勇[1,2] 

机构地区：[1]四川大学华西药学院药物化学系,成都610041 [2]四川大学华西药学院靶向药物及释药系统教育部重点实验室,成都610041

出　　处：《有机化学》2013年第3期621-629,共9页Chinese Journal of Organic Chemistry

基　　金：国家自然科学基金(Nos.20672077;20872099);教育部博士点基金(No.20110181110079);国家科技重大专项(No.2013ZX09301304-002)资助项目~~

摘　　要：基于多靶点药物设计策略,以染料木素为先导化合物,对其7-位和4'-位羟基进行修饰,合成了24个染料木素氨基甲酸酯类衍生物,其化学结构经1H NMR和HRMS确证.生物活性测试结果表明,部分化合物对乙酰胆碱酯酶具有较强抑制活性,且对H2O2诱导的PC12细胞氧化损伤具有显著保护作用.With genistein as lead compound, twenty-four genistein carbamate derivatives were synthesized from genistein with the structural modification of 7-OH and 4＇-OH based on the muti-target-directed drug design strategy. The chemical structures of target compounds were confirmed by 1H NMR and HRMS techniques. Their acetylcholinesterase and butylcho- linesterase inhibitory activity and neuroprotective effects against hydrogen peroxide induced PC12 cell injury were evaluated in vitro. The results indicated that some compounds exhibited the most potent acetylcholinesterase inhibitory activity and neuroprotective effects.

关 键 词：阿尔茨海默症 多靶点药物治疗 染料木素氨基甲酸酯类衍生物 合成 乙酰胆碱酯酶抑制剂 神经保护剂 

分 类 号：TQ463[化学工程—制药化工]