3D-QSAR studies and molecular docking on [5-(4-amino-1<Emphasis Type="Italic">H</Emphasis>-benzoimidazol-2-yl)-furan-2-yl]-phosphonic acid derivatives as fructose-1,6-biphophatase inhibitors |
| |
Authors: | Ping Lan Mei-Qi Xie Yue-Mei Yao Wan-Na Chen Wei-Min Chen |
| |
Institution: | (1) Guangdong Province Key Laboratory of Pharmacodynamic Constituents of TCM and New Drugs Research, College of Pharmacy, Jinan University, 510632 Guangzhou, People’s Republic of China; |
| |
Abstract: | Fructose-1,6-biphophatase has been regarded as a novel therapeutic target for the treatment of type 2 diabetes mellitus (T2DM).
3D-QSAR and docking studies were performed on a series of 5-(4-amino-1H-benzoimidazol-2-yl)-furan-2-yl]-phosphonic acid derivatives as fructose-1,6-biphophatase inhibitors. The CoMFA and CoMSIA
models using thirty-seven molecules in the training set gave r
cv2 values of 0.614 and 0.598, r
2 values of 0.950 and 0.928, respectively. The external validation indicated that our CoMFA and CoMSIA models possessed high
predictive powers with r
02 values of 0.994 and 0.994, r
m2 values of 0.751 and 0.690, respectively. Molecular docking studies revealed that a phosphonic group was essential for binding
to the receptor, and some key features were also identified. A set of forty new analogues were designed by utilizing the results
revealed in the present study, and were predicted with significantly improved potencies in the developed models. The findings
can be quite useful to aid the designing of new fructose-1,6-biphophatase inhibitors with improved biological response. |
| |
Keywords: | |
本文献已被 PubMed SpringerLink 等数据库收录! |
|