染料木素氨基甲酸酯类衍生物的合成及生物活性研究有机化学.pdfVIP

DOI: 10.6023/cjoc201210042 研究论文 有机化学 Chinese Journal of Organic Chemistry ARTICLE 染料木素氨基甲酸酯类衍生物的合成及生物活性研究 强晓明a 袁 文a 桑志培a 邓 勇*,a,b (a 四川大学华西药学院药物化学系 成都 610041) (b 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) 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. 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 Synthesis and Biological Evaluation of Genistein Carbamate Derivatives Qiang, Xiaominga Yuan, Wena Sang, Zhipeia Deng, Yong*,a,b a ( Department of Medicinal Chemistry, West China School of Pharmacy, Sichuan University, Chengdu 610041) b ( Key Laboratory of Drug Targeting and Drug Delivery System, Ministry of Education, West China School of Pharmacy, Sichuan University, Chengdu 610041) Abstract 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 ind