薯蓣皂苷元衍生物与M_3受体的分子对接研究  

Molecular docking study of diosgenin derivatives and M_3 receptor

作　　者：万剑飞[1] 刘超[1] 王珍珍 包旭[1] 范举正[1] 

机构地区：[1]四川大学华西药学院,四川成都610041 [2]上海浦东新区睿智化学研究有限公司,上海210201

出　　处：《华西药学杂志》2012年第3期244-246,共3页West China Journal of Pharmaceutical Sciences

摘　　要：目的研究薯蓣皂苷元衍生物与M3受体相互作用可能的构效关系,为薯蓣皂苷元舒张平滑肌的结构改造提供更多的理论基础。方法运用AutoDock4.0研究薯蓣皂苷元衍生物与M3受体的分子对接,并分析了对接结果与薯蓣皂苷元衍生物对离体豚鼠气管平滑肌舒张活性的结果,对接模型中的M3受体分子模型为以牛视紫红质的晶体结构为模板同源建模搭建的人M3受体的三维结构模型。结果薯蓣皂苷元衍生物与M3受体的对接结果与离体豚鼠气管平滑肌舒张的活性结果有一定联系。结论薯蓣皂苷元衍生物Ⅰ～Ⅴ的舒张活性有在一定范围内随碳链增长而提高的趋势;芳香酯类(Ⅵ～Ⅸ)的舒张活性可能与苯环取代基的供电性有关;带苯环的支链酯类(Ⅹ～Ⅺ)的位阻可能对舒张活性影响较大。因此,薯蓣皂苷元衍生物与M3受体的对接对其进一步的修饰有一定的指导作用。OBJECTIVE To study certain structure-activity relationships between diosgenin derivatives and M3 receptor which may provide more theoretical basis for further modification of diosgenin.METHODS CADD software Autodock 4.0 was employed in the study of molecular docking between diosgenin derivatives and muscarinic M3 receptor（M3）.The 3D molecular model of M3 receptor（resolution ratio 2.80 nm,PDB number 1F88） was kindly provided by Giulio Vistoli which was built by homology modeling methods from the crystal structure of bovine rhodopsin.RESULTS The effects of diosgenin derivatives on isolated tracheal smooth muscles of guinea pigs and the docking results between diosgenin derivatives and muscarinic M3 receptor showed that there were certain relationships between their activities and their inhibition constant（Ki）.CONCLUSION For the derivatives（compound 1-5）,there was an increasing trend in activity with longer carbon chain.The activities of compound 6-9 may be effected by the different aromatic substituting groups.For the compound 10-11,the steric hindrance of their aromatic substituting groups may have a larger impact on activities.Consequently,the molecular docking study between diosgenin derivatives and M3 receptor may provide a guidance role for further structural modification of diosgenin.

关 键 词：薯蓣皂苷元衍生物 分子对接 M3受体 定量构效关系 

分 类 号：R914[医药卫生—药物化学]