3D-QSAR and molecular docking studies of quinazoline derivatives as glycogen synthase kinase-3?2 (Gsk-3?2) inhibitors

摘要

The discovery of glycogen synthase kinase-3β (GSK3β) inhibitors has proven to be challenging task to identify novel and potent gsk3β inhibitors. The quantitative structure activity relationship (QSAR) and docking approach became very useful and largely widespread technique for ligand-based drug design. The computational study deals with development of 3D QSAR models for 85 selected quinazoline derivatives using the stepwise variable selection knearest neighbor molecular field analysis approach; a leave-one-out cross validation method. The developed model showed satisfactory statistical significance r2 (Regression) with 0.75 and q2 (Correlation coefficient) 0.81. Further we have carried out molecular docking studies with the x-ray crystal structure of glycogen synthase kinase domain. These studies showed that quinazoline scaffold can be utilized for designing of novel GSK-3β inhibitors.