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DICP OpenIR  > 中国科学院大连化学物理研究所  > 期刊论文
学科主题: 物理化学
题名: In Silico Identification of Structure Requirement for Novel Thiazole and Oxazole Derivatives as Potent Fructose 1,6-Bisphosphatase Inhibitors
作者: Hao, Ming1;  Zhang, Xiaole2;  Ren, Hong3, 4;  Li, Yan1;  Zhang, Shuwei1;  Luo, Fang5;  Ji, Mingjuan5;  Li, Guohui4;  Yang, Ling6
通讯作者: 李燕
关键词: 3D-QSAR ;  molecular dynamics ;  FBPase inhibitors ;  CoMFA ;  CoMSIA
刊名: INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
发表日期: 2011-11-01
DOI: 10.3390/ijms12118161
卷: 12, 期:11, 页:8161-8180
收录类别: SCI
文章类型: Article
部门归属: 11;18
项目归属: 1106;1806
产权排名: 4,3
WOS标题词: Science & Technology ;  Physical Sciences
类目[WOS]: Chemistry, Multidisciplinary
摘要: In Silico Identification of Structure Requirement for Novel Thiazole and Oxazole Derivatives as Potent Fructose 1,6-Bisphosphatase Inhibitors
研究领域[WOS]: Chemistry
英文摘要: Fructose 1,6-bisphosphatase (FBPase) has been identified as a drug discovery target for lowering glucose in type 2 diabetes mellitus. In this study, a large series of 105 FBPase inhibitors were studied using a combinational method by 3D-QSAR, molecular docking and molecular dynamics simulations for a further improvement in potency. The optimal 3D models exhibit high statistical significance of the results, especially for the CoMFA results with r(ncv)(2), q(2) values of 0.986, 0.514 for internal validation, and r(pred)(2), r(m)(2) statistics of 0.902, 0.828 statistics for external validation. Graphic representation of the results, as contoured 3D coefficient plots, also provides a clue to the reasonable modification of molecules. (1) Substituents with a proper length and size at the C5 position of the thiazole core are required to enhance the potency; (2) A small and electron-withdrawing group at the C2 position linked to the thiazole core is likely to help increase the FBPase inhibition; (3) Substituent groups as hydrogen bond acceptors at the C2 position of the furan ring are favored. In addition, the agreement between 3D-QSAR, molecular docking and molecular dynamics simulation proves the rationality of the developed models. These results, we hope, may be helpful in designing novel and potential FBPase inhibitors.
关键词[WOS]: PARTICLE MESH EWALD ;  MOLECULAR DOCKING ;  AMP MIMICS ;  ALLOSTERIC SITE ;  FRUCTOSE-1,6-BISPHOSPHATASE ;  MODELS ;  QSAR ;  GLUCONEOGENESIS ;  SELECTION ;  VALIDATION
语种: 英语
WOS记录号: WOS:000297696100060
Citation statistics: 
内容类型: 期刊论文
URI标识: http://cas-ir.dicp.ac.cn/handle/321008/115701
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.Dalian Univ Technol, Dept Mat Sci & Chem Engn, Dalian 116023, Liaoning, Peoples R China
2.Dalian Univ Technol, Dept Math Sci, Dalian 116023, Liaoning, Peoples R China
3.Shandong Univ, Sch Med, Qi Lu Hosp, Dept Ophthalmol, Jinan 250012, Peoples R China
4.Chinese Acad Sci, Dalian Inst Chem Phys, Lab Mol Modeling & Design, State Key Lab Mol React Dynam, Dalian 116023, Liaoning, Peoples R China
5.Chinese Acad Sci, Grad Sch, Coll Chem & Chem Engn, Beijing 100049, Peoples R China
6.Chinese Acad Sci, Dalian Inst Chem Phys, Lab Pharmaceut Resource Discovery, Grad Sch, Dalian 116023, Liaoning, Peoples R China

Recommended Citation:
Hao, Ming,Zhang, Xiaole,Ren, Hong,et al. In Silico Identification of Structure Requirement for Novel Thiazole and Oxazole Derivatives as Potent Fructose 1,6-Bisphosphatase Inhibitors[J]. INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES,2011,12(11):8161-8180.
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