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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 the possible structure-activity relationship of the interaction between diosgenin derivatives and M3 receptors and to provide more theoretical basis for the structural modification of diosgenin. Methods The molecular docking of diosgenin derivatives and M3 receptors was studied by using AutoDock4.0. The docking results and the relaxation activities of diosgenin derivatives on the tracheal smooth muscle of isolated guinea pigs were analyzed. The molecular models of M3 receptor in the docked model It is a three-dimensional structural model of human M3 receptor that is constructed by homology modeling with bovine rhodopsin crystal structure as a template. Results The docking results of diosgenin derivatives and M3 receptors were correlated with the activity of isolated vasodilator smooth muscle in guinea pigs. Conclusion The diastolic activity of diosgenin derivatives Ⅰ ~ Ⅴ increased with the increase of carbon chain within a certain range. The diastolic activity of aromatic esters (Ⅵ ~ Ⅸ) may be related to the chargeability of benzene ring substituents. Steric hindrance of the branched chain esters of the ring (X-Ⅺ) may have a greater effect on the diastolic activity. Therefore, the docking of diosgenin derivatives with M3 receptors may provide some guidance for their further modification.