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;刘超;王珍珍;包旭;范举正;
Author：
收稿日期： 年卷（期）页码：2012,27(03):-244-246
期刊名称：华西药学杂志
Journal Name：WEST CHINA JOURNAL OF PHARMACEUTICAL SCIENCES
关键字：薯蓣皂苷元衍生物;分子对接;M3受体;定量构效关系
Key words：
基金项目：
中文摘要
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。
参考文献
[1]Yang CM,Chou SP,Sung TC.Muscarinic receptor subtypes cou-pled to generation of different second messengers in isolated tra-cheal smooth muscle cells[J].Br J Pharmacol,1991,104(3):613-618.
[2]Elizabeth AT,Frederick JE.Involvement of the M2 muscarinic re-ceptor in contractions of the guinea pig trachea,guinea pig esoph-agus,and rat fundus[J].Bioche Pharmac,1996,51:779-788.
[3]刘超,王珍珍,郑微,等.薯蓣皂苷元衍生物的制备及对豚鼠离体气管平滑肌的作用[J].华西药学杂志,2009,24(5):483-486.
[4]耿倩,曾春玲,傅微微,等.薯蓣皂苷元衍生物的制备及其抗肿瘤活性[J].华西药学杂志,2009,24(5):475-478.
[5]Alessandro P,Giulio V,Cristina M,et al.Muscarinic receptors:Acomparative analysis of structural features and binding modesthrough homology modeling and molecular docking[J].Chem&Biodi,2006,3:481-501.
[6]Edward CH,Carol AMC,Karen MP,et al.The role of charge in-teractions in muscarinic agonist binding,and receptor-responsecoupling[J].Life Sci,1995,56:891-898.
[7]Liliana O,Maria M,Mircea M,et al.Exploring the binding site ofthe human muscarinic M3 receptor:Homology modeling and doc-king study[J].Inter J Quantum Chemi,2007,107:1794-1802.
[8]Jana S,Wolfgang B,Dirk P,et al.Enantiomeric N-methyl-4-piperidyl benzilates as muscarinic receptor ligands:Radioligandbinding studies and docking studies to models of the three musca-rinic receptors M1,M2 and M3[J].Bioorganic&Med Chem,2006,14:1729-1736.
[9]Morris GM,Goodsell DS,Halliday RS.Automatedocking using alamarckian genetic algorithm and anempirical binding free energyfunction[J].J Comput Chem,1998,19:1639-1662.
[10]Pettersen EF,Goddard TD,Huang CC,et al.UCSF Chimera-avisualization system for exploratory research and analysis[J].JComput Chem,2004,25(13):1605-1612.
[11]Sanner MF,Duncan BS,Carrillo CJ,et al.Integrating computationand visualization for biomolecular analysis:An example usingPython and AVS[J].Proc Pac Symp Biocomp,1998,99:401-412.
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