title: CoMFA and CoMSIA studies on C-aryl glucoside SGLT2 inhibitors as potential anti-diabetic agents.
abstract: SGLT2 has become a target of therapeutic interest in diabetes research. CoMFA and CoMSIA studies were performed on C-aryl glucoside SGLT2 inhibitors (180 analogues) as potential anti-diabetic agents. Three different alignment strategies were used for the compounds. The best CoMFA and CoMSIA models were obtained by means of Distill rigid body alignment of training and test sets, and found statistically significant with cross-validated coefficients (q²) of 0.602 and 0.618, respectively, and conventional coefficients (r²) of 0.905 and 0.902, respectively. Both models were validated by a test set of 36 compounds giving satisfactory predicted correlation coefficients (r² pred) of 0.622 and 0.584 for CoMFA and CoMSIA models, respectively. A comparison was made with earlier 3D QSAR study on SGLT2 inhibitors, which shows that our 3D QSAR models are better than earlier models to predict good inhibitory activity. CoMFA and CoMSIA models generated in this work can provide useful information to design new compounds and helped in prediction of activity prior to synthesis.
authors.affiliation: Department of Pharmaceutical Chemistry, Nirma University, Ahmedabad, India. vicky_1744@yahoo.com
authors.forename: V K
authors.initials: VK
authors.lastname: Vyas
authors.forename: H G
authors.initials: HG
authors.lastname: Bhatt
authors.forename: P K
authors.initials: PK
authors.lastname: Patel
authors.forename: J
authors.initials: J
authors.lastname: Jalu
authors.forename: C
authors.initials: C
authors.lastname: Chintha
authors.forename: N
authors.initials: N
authors.lastname: Gupta
authors.forename: M
authors.initials: M
authors.lastname: Ghate
mesh_terms: D004791:Enzyme Inhibitors / Q000737:chemistry* / Q000494:pharmacology*; D005960:Glucosides / Q000737:chemistry* / Q000494:pharmacology*; D007004:Hypoglycemic Agents / Q000494:pharmacology*; D015394:Molecular Structure; D021281:Quantitative Structure-Activity Relationship; D000077203:Sodium-Glucose Transporter 2 Inhibitors
chemical_list: D004791:Enzyme Inhibitors; D005960:Glucosides; D007004:Hypoglycemic Agents; D000077203:Sodium-Glucose Transporter 2 Inhibitors