23-羟基白桦酸衍生物抗肿瘤作用的三维定量构效关系及分子对接模式探索研究  

3D-QSAR and Molecular Docking Studies on 23-Hydroxybetulinic Acid Derivatives with Antitumor Activity

作　　者：张婷婷[1] 毕毅[1] 陈蒙蒙[1] 张晓晨[1] 徐进宜[2] 吴晓明[2] 

机构地区：[1]烟台大学药物化学教研室,山东烟台264005 [2]中国药科大学天然药物活性组分与药效国家重点实验室,南京210009

出　　处：《中国药学杂志》2014年第14期1200-1204,共5页Chinese Pharmaceutical Journal

基　　金：国家自然科学基金资助项目(81001358;81273377);2014年烟台大学研究生科技创新基金项目重点项目(YJSZ201420);2013年度烟台大学青年基金项目

摘　　要：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 formulate the three-dimensional quantitative structure-activity relationship （3D-QSAR） model of 23- hydroxybetulinic acid derivatives with promising antitumor activity and study their molecular docking with topoisomerase I （Topo I）. METHODS Topomer CoMFA was used to analyze the quantitative structure-activity relationship of thirty-four 23-hydroxybetulinic acid derivatives, and molecular docking analysis was applied to characterize the interactions between 23-hydroxybetulinic acid derivatives and Topo I. RESULTS One satisfactory substructure-based Topomer CoMFA model （q2,0. 521 ; r2 , 0. 873 ） possessing predictive capability was obtained. Surflex-dock analysis displayed that the ligands and Topo I interacted with each other via several residues （such as Lys532, Arg488, Arg590 and Arg364） which had a very important effect on hydrogen bonds. CONCLUSION Topomer CoMFA combined with Surflex-dock analysis can be applied to design new 23-hydroxybetulinic acid derivatives with higher antitumor activities.

关 键 词：23-羟基白桦酸 三维定量构效关系模型 分子对接 拓扑异构酶I 抗肿瘤活性 

分 类 号：R914.2[医药卫生—药物化学]