3D-QSAR studies and molecular docking on [5-(4-amino-1H-benzoimidazol-2-yl)-furan-2-yl]-phosphonic acid derivatives as fructose-1,6-biphophatase inhibitors

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 (cv) (2) 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 (0) (2) values of 0.994 and 0.994, r (m) (2) 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.

Molecular Modeling Studies on 11H-Dibenz[b,e]azepine and Dibenz[b,f][1,4]oxazepine Derivatives as Potent Agonists of the Human TRPA1 Receptor

“…In this equation, SD is the sum of the squared deviations between the agonistic activities of the test set and the mean activity of the training molecules and PRESS is the sum of squared deviations between predicted and actual activity values for each molecule in the test set [ 13 , 24 , 25 , 26 ].…”

Structure-based ensemble-QSAR model: a novel approach to the study of the EGFR tyrosine kinase and its inhibitors

“…However, proteins are dynamically flexible macromolecules, and different structures of a protein may show different recognition abilities towards even the same ligand. Although ensemble docking has shown some advantages in improving the enrichment factor or diversity [22,23] , to our knowledge, all docking-based 3D-QSAR studies still use a single crystal structure for ligand pose prediction [17,24,25] . However, the recognition ability of a protein structure towards inhibitors with different chemical types is rarely explored.…”

High performance screening, structural and molecular dynamics analysis to identify H1 inhibitors from TCM Database@Taiwan

“…This class of medicine has been introduced as alternative medicine complementary to western medicine. TCM has high therapeutic values such as anti-tumor growth, [16][17][18][19] anti-diabetes, [20][21][22][23] and anti-metastasis functions. 24,25 In addition, high throughput in silico pharmacology has been employed for TCM drug discovery against chronic disorders such as insomnia, allergy, stroke, cancer, and many more.…”