In Silico Identification of Structure Requirement for Novel Thiazole and Oxazole Derivatives as Potent Fructose 1,6-Bisphosphatase Inhibitors
文献类型：期刊论文
| 作者 | Hao, Ming1; Zhang, Xiaole2; Ren, Hong3,4; Li, Yan1; Zhang, Shuwei1; Luo, Fang5; Ji, Mingjuan5; Li, Guohui4; Yang, Ling6 |
| 刊名 | international journal of molecular sciences
 |
| 出版日期 | 2011-11-01 |
| 卷号 | 12期号:11页码:8161-8180 |
| 关键词 | 3D-QSAR molecular dynamics FBPase inhibitors CoMFA CoMSIA |
| ISSN号 | 待补充 |
| 产权排序 | 4,3 |
| 通讯作者 | 李燕 |
| 中文摘要 | in silico identification of structure requirement for novel thiazole and oxazole derivatives as potent fructose 1,6-bisphosphatase inhibitors |
| 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. |
| WOS标题词 | science & technology ; physical sciences |
| 学科主题 | 物理化学 |
| 类目[WOS] | chemistry, multidisciplinary |
| 研究领域[WOS] | chemistry |
| 关键词[WOS] | particle mesh ewald ; molecular docking ; amp mimics ; allosteric site ; fructose-1,6-bisphosphatase ; models ; qsar ; gluconeogenesis ; selection ; validation |
| 收录类别 | SCI |
| 语种 | 英语 |
| WOS记录号 | WOS:000297696100060 |
| 公开日期 | 2012-07-09 |
| 源URL | [http://159.226.238.44/handle/321008/115701]  |
| 专题 | 大连化学物理研究所_中国科学院大连化学物理研究所 |
| 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 |
| 推荐引用方式 GB/T 7714 | 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. |
| APA | Hao, Ming.,Zhang, Xiaole.,Ren, Hong.,Li, Yan.,Zhang, Shuwei.,...&Yang, Ling.(2011).In Silico Identification of Structure Requirement for Novel Thiazole and Oxazole Derivatives as Potent Fructose 1,6-Bisphosphatase Inhibitors.international journal of molecular sciences,12(11),8161-8180. |
| MLA | Hao, Ming,et al."In Silico Identification of Structure Requirement for Novel Thiazole and Oxazole Derivatives as Potent Fructose 1,6-Bisphosphatase Inhibitors".international journal of molecular sciences 12.11(2011):8161-8180. |
入库方式： OAI收割
来源：大连化学物理研究所
浏览0
下载0
收藏0
其他版本
除非特别说明，本系统中所有内容都受版权保护，并保留所有权利。