欧前胡素衍生物的合成与血管舒张活性研究  

Research on the synthesis and vasodilatation activity of imperatorin derivatives

作　　者：黄立敏 李友佳[2] 侯亚静 王程 魏迪 贺怀贞[1] HUANG Limin;LI Youjia;HOU Yajing;WANG Cheng;WEI Di;HE Huaizhen(School of Pharmacy,Xi'an Jiaotong University,Xi’an 710061,China;The Second Affiliated Hospital of Xi’an Jiao tong University,Xi’an 710004,China)

机构地区：[1]西安交通大学药学院,西安710061 [2]西安交通大学第二附属医院,西安710004

出　　处：《西北药学杂志》2018年第1期87-91,共5页Northwest Pharmaceutical Journal

基　　金：陕西省自然科学基础研究计划项目(编号:2016JM8076)

摘　　要：目的合成欧前胡素衍生物,考察所得化合物的血管舒张活性。方法在保留欧前胡素(IMP)母核结构的基础上,设计合成4个欧前胡素衍生物;采用多通道微血管张力测定法,对所得化合物的活性进行考察;应用计算机辅助药物设计软件,对所得化合物与可能靶标蛋白的相互作用进行分析。结果所得欧前胡素衍生物在不同动脉血管上均有不同程度的舒张效应。结论通过优化Williamson醚化反应条件,合成4个欧前胡素衍生物,反应步骤简单,条件温和。其中化合物5的3种血管舒张效应最好。进一步分子对接研究表明,化合物5与可能作用受体有较好的亲和力,为欧前胡素衍生物的结构优化提供理论依据。Imperatorin derivatives were designed,synthesized and screened for their vasodilatation activity.4 imperatorin derivatives were designed and synthesized based on the structure modification of imperatorin.Their vasodilatory activities were screened by multichannel microvascular strain determination method.The interactions between compounds and potential target proteins were analyzed by computer aided drug design software.Imperatorin derivatives exhibited different degrees of vasodilatation activity in different blood vessels.In this research,the imperatorin derivatives were synthesized by optimizing the Williamson reaction with simple procedure and mild conditions.4 compounds all exhibited certain vasodilatation activity.Among them,compound 5 possessed the best activity.Further molecular docking research also indicated that compound 5 had a better affinity with the potential target proteins.This study provided theoretical basis for optimizing the structure of imperatorin in the future research.

关 键 词：欧前胡素 合成 血管舒张活性 分子对接 

分 类 号：R914.2[医药卫生—药物化学]