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目的探索具有抗肿瘤作用的23-羟基白桦酸衍生物的三维定量构效关系模型,及其与拓扑异构酶I(Topo I)的分子对接模式。方法本实验应用Topomer CoMFA,对34个23-羟基白桦酸衍生物进行定量构效关系研究,建立三维定量构效关系模型。根据文献,采用Surflex-dock研究23-羟基白桦酸衍生物与拓扑异构酶I的分子对接结合模式。结果 Topomer CoMFA模型q2=0.521,r2=0.873,建立了预测能力较好的三维定量关系模型。Surflex-dock结果显示,此类分子与Topo I的Lys532、Arg488、Arg590、Arg364等活性功能残基具有氢键作用。结论所建三维定量构效关系模型预测能力较好,可用于指导23-羟基白桦酸衍生物的设计。分子对接结果显示,Topo I可以作为23-羟基白桦酸衍生物抗肿瘤活性的潜在靶点进行实验室研究。
Objective To explore the three-dimensional quantitative structure-activity relationship model of 23-hydroxy betulinic acid derivatives with anti-tumor effect and its molecular docking mode with Topo I. Methods In this study, Topomer CoMFA was used to study the quantitative structure-activity relationship of 34 23-hydroxy-betulinic acid derivatives and to establish a three-dimensional quantitative structure-activity relationship model. According to the literature, Surflex-dock was used to study the mode of molecular docking of 23-hydroxy betulinic acid derivatives to topoisomerase I. Results Topomer CoMFA model q2 = 0.521, r2 = 0.873, and a three-dimensional quantitative relationship model with good predictive ability was established. Surflex-dock results show that these molecules have a hydrogen bond with the active functional residues of Topo I such as Lys532, Arg488, Arg590, Arg364. Conclusion The constructed three-dimensional quantitative structure-activity relationship model has good predictive ability and can be used to guide the design of 23-hydroxy betulinic acid derivatives. The molecular docking results show that Topo I can be used as a potential target for the anti-tumor activity of 23-hydroxy betulinic acid derivatives in laboratory studies.