QSAR analysis of sodium glucose co-transporter 2 (SGLT2) inhibitors for anti-hyperglycaemic lead development.
QSAR (Quantitative Structure Activity Relationship) modelling was performed on a dataset of 90 sodium-dependent glucose cotransporter 2 (SGLT2) inhibitors. The quantitative and explicative evaluations revealed some of the subtle and distinguished structural features that are responsible for the inhibitory potency of these compounds against SGLT2, such as less possible number of ring carbons at 8 Å from the lipophilic atoms in the molecule (fringClipo8A) and more possible value for the sum of the partial charges of the lipophilic atoms present within seven bonds from the donor atoms (lipo_don_7Bc). Multivariate GA-MLR (genetic algorithm-multi linear regression) and thorough validation methodology out-turned a statistically robust QSAR model with a very high predictability shown from various statistical parameters. A QSAR model with r2 = 0.83, F = 51.54, Q2LOO = 0.79, Q2LMO = 0.79, CCCcv = 0.88, Q2Fn = 0.76-0.81, r2ext = 0.77, CCCext = 0.85, and with RMSEtr < RMSEcv was proposed. This QSAR model will assist synthetic chemists in the development of the SGLT2 inhibitors as the antidiabetic leads.
['Gandhi|A|A|', 'Masand|V|V|', 'Zaki|M E A|MEA|', 'Al-Hussain|S A|SA|', 'Ghorbal|A Ben|AB|', 'Chapolikar|A|A|']
D062126:Databases, Chemical D005960:Glucosides D016014:Linear Models D021281:Quantitative Structure-Activity Relationship D000077203:Sodium-Glucose Transporter 2 Inhibitors
QSAR SGLT2 T1DM T2DM hyperglycaemia