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

张婷婷,毕毅*,陈蒙蒙,张晓晨,徐进宜,吴晓明*

中国药学杂志 ›› 2014, Vol. 49 ›› Issue (14) : 1200-1204.

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中国药学杂志 ›› 2014, Vol. 49 ›› Issue (14) : 1200-1204. DOI: 10.11669/cpj.2014.14.005
论著

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

  • 张婷婷1,毕毅1*,陈蒙蒙1,张晓晨1,徐进宜2,吴晓明2*
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3D-QSAR and Molecular Docking Studies on 23-Hydroxybetulinic Acid Derivatives with Antitumor Activity

  • ZHANG Ting-ting1, BI Yi1*, CHEN Meng-meng1, ZHANG Xiao-chen1,XU Jin-yi2, WU Xiao-ming2*
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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。

Abstract

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

Key words

23-hydroxybetulinic acid derivatives / topomer CoMFA / surflex-dock / Topo I / antitumor activity

引用本文

导出引用
张婷婷,毕毅*,陈蒙蒙,张晓晨,徐进宜,吴晓明*. 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[J]. 中国药学杂志, 2014, 49(14): 1200-1204 https://doi.org/10.11669/cpj.2014.14.005
ZHANG Ting-ting, BI Yi*, CHEN Meng-meng, ZHANG Xiao-chen,XU Jin-yi, WU Xiao-ming*. 3D-QSAR and Molecular Docking Studies on 23-Hydroxybetulinic Acid Derivatives with Antitumor Activity[J]. Chinese Pharmaceutical Journal, 2014, 49(14): 1200-1204 https://doi.org/10.11669/cpj.2014.14.005
中图分类号: R914.2   

参考文献

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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
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