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学科主题: 物理化学
题名: Induced-fit docking and binding free energy calculation on furostanol saponins from Tupistra chinensis as epidermal growth factor receptor inhibitors
作者: Luo, Hua-Jun1;  Wang, Jun-Zhi1;  Deng, Wei-Qiao2;  Zou, Kun1
通讯作者: Hua-Jun Luo
关键词: Furostanol saponins ;  Induced-fit docking ;  EGFR ;  Binding free energy
刊名: MEDICINAL CHEMISTRY RESEARCH
发表日期: 2013-10-01
DOI: 10.1007/s00044-013-0509-4
卷: 22, 期:10, 页:4970-4979
收录类别: SCI
合作性质: 
文章类型: Article
部门归属: 11
项目归属: 11T4
产权排名: 待补充
WOS标题词: Science & Technology ;  Life Sciences & Biomedicine
类目[WOS]: Chemistry, Medicinal
资助者: 2,3
研究领域[WOS]: Pharmacology & Pharmacy
英文摘要: Three furostanol saponins isolated from Tupistra chinensis were studied to investigate the reasons for their different inhibitory activities toward non-small-cell lung cancer (NSCLC) A549 cell using induced-fit docking (IFD) between them and epidermal growth factor receptor (EGFR). Their binding free energies were also calculated by molecular mechanics-generalized Born surface area (MM-GBSA) method. The calculation results were all in excellent agreement with experimental activities (IC50 values of compound 1-3 against NSCLC A549 cell: 6.6, 6.7, and 29.1 mu M). With EGFR (PDB code: 1M17 and 2ITY), the docking IFD score, binding free energy, and binding free energy neglecting the effect of entropy contributions of compound 1 ((25R)-26-O-beta-d-glucopyranosyl-furost-1 beta,3 beta,22 alpha,26-tetrahydroxy-3-O-beta-d-glucopyranoside) were -553.9223, -59.6101, and -70.8088 kcal/mol in 1M17 (-536.2678, -62.2158, and -68.4053 kcal/mol in 2ITY), respectively. The binding sites of compound 1 are similar to erlotinib in 1M17 and gefitinib in 2ITY. There are two hydrogen bonds between compound 1 and the key amino acid residue Met769 in 1M17 or Met793 in 2ITY. The only structure difference between compound 3 and compound 1 is 5-hydroxyl polar group in compound 3, which hinders the hydrophobic interactions with EGFR and increases polar solvation free energy term that opposes binding. This indicates that compound 1 could be a potent EGFR inhibitor for NSCLC treatment.
关键词[WOS]: LUNG-CANCER ;  STRUCTURAL ELUCIDATION ;  BIOLOGICAL EVALUATION ;  KINASE INHIBITORS ;  EGFR ;  COMPLEX ;  GEFITINIB ;  PROTEINS ;  RHIZOMES ;  THERAPY
语种: 英语
原文出处: 查看原文
WOS记录号: WOS:000323665600042
Citation statistics: 
内容类型: 期刊论文
URI标识: http://cas-ir.dicp.ac.cn/handle/321008/119422
Appears in Collections:中国科学院大连化学物理研究所_期刊论文

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作者单位: 1.China Three Gorges Univ, Coll Chem & Life Sci, Hubei Key Lab Nat Prod Res & Dev, Yichang 443002, Hubei, Peoples R China
2.Chinese Acad Sci, Dalian Inst Chem Phys, Dalian 116023, Liaoning, Peoples R China

Recommended Citation:
Luo, Hua-Jun,Wang, Jun-Zhi,Deng, Wei-Qiao,et al. Induced-fit docking and binding free energy calculation on furostanol saponins from Tupistra chinensis as epidermal growth factor receptor inhibitors[J]. MEDICINAL CHEMISTRY RESEARCH,2013,22(10):4970-4979.
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