In Silico Identification of Structure Requirement for Novel Thiazole and Oxazole Derivatives as Potent Fructose 1,6-Bisphosphatase Inhibitors
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...
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Molecular Diversity Preservation International (MDPI)
2011
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| Online Access: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3233463/ |
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pubmed-32334632011-12-15 In Silico Identification of Structure Requirement for Novel Thiazole and Oxazole Derivatives as Potent Fructose 1,6-Bisphosphatase Inhibitors Hao, Ming Zhang, Xiaole Ren, Hong Li, Yan Zhang, Shuwei Luo, Fang Ji, Mingjuan Li, Guohui Yang, Ling Article 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 rncv2, q2 values of 0.986, 0.514 for internal validation, and rpred2, rm2 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. Molecular Diversity Preservation International (MDPI) 2011-11-18 /pmc/articles/PMC3233463/ /pubmed/22174657 http://dx.doi.org/10.3390/ijms12118161 Text en © 2011 by the authors; licensee MDPI, Basel, Switzerland. http://creativecommons.org/licenses/by/3.0 This article is an open-access article distributed under the terms and conditions of the Creative Commons Attribution license (http://creativecommons.org/licenses/by/3.0/). |
| repository_type |
Open Access Journal |
| institution_category |
Foreign Institution |
| institution |
US National Center for Biotechnology Information |
| building |
NCBI PubMed |
| collection |
Online Access |
| language |
English |
| format |
Online |
| author |
Hao, Ming Zhang, Xiaole Ren, Hong Li, Yan Zhang, Shuwei Luo, Fang Ji, Mingjuan Li, Guohui Yang, Ling |
| spellingShingle |
Hao, Ming Zhang, Xiaole Ren, Hong Li, Yan Zhang, Shuwei Luo, Fang Ji, Mingjuan Li, Guohui Yang, Ling In Silico Identification of Structure Requirement for Novel Thiazole and Oxazole Derivatives as Potent Fructose 1,6-Bisphosphatase Inhibitors |
| author_facet |
Hao, Ming Zhang, Xiaole Ren, Hong Li, Yan Zhang, Shuwei Luo, Fang Ji, Mingjuan Li, Guohui Yang, Ling |
| author_sort |
Hao, Ming |
| title |
In Silico Identification of Structure Requirement for Novel Thiazole and Oxazole Derivatives as Potent Fructose 1,6-Bisphosphatase Inhibitors |
| title_short |
In Silico Identification of Structure Requirement for Novel Thiazole and Oxazole Derivatives as Potent Fructose 1,6-Bisphosphatase Inhibitors |
| title_full |
In Silico Identification of Structure Requirement for Novel Thiazole and Oxazole Derivatives as Potent Fructose 1,6-Bisphosphatase Inhibitors |
| title_fullStr |
In Silico Identification of Structure Requirement for Novel Thiazole and Oxazole Derivatives as Potent Fructose 1,6-Bisphosphatase Inhibitors |
| title_full_unstemmed |
In Silico Identification of Structure Requirement for Novel Thiazole and Oxazole Derivatives as Potent Fructose 1,6-Bisphosphatase Inhibitors |
| title_sort |
in silico identification of structure requirement for novel thiazole and oxazole derivatives as potent fructose 1,6-bisphosphatase inhibitors |
| description |
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 rncv2, q2 values of 0.986, 0.514 for internal validation, and rpred2, rm2 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. |
| publisher |
Molecular Diversity Preservation International (MDPI) |
| publishDate |
2011 |
| url |
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3233463/ |
| _version_ |
1611492689350492160 |