SYNTHESIS & PREDICTING THE POSSIBILITY OF 2, 5-DISUBSTITUTED-1, 3, 4-OXADIAZOLE DERIVATIVES AS GSK- 3β INHIBITORSAbstract
A new series of 2, 5-disubstituted-1, 3, 4-oxadiazole derivatives were synthesized using appropriate methods & structures of the synthesized compounds were confirmed by IR,NMR & Mass spectral data.. These ligands were prefiltered for their drug likeness properties by Lipinski’s rule of 5 and it was found that all the ligands satisfied the rule of 5 for oral bioavailability.The prefiltered ligands were subjected for docking studies using integrated web server called docking server to investigate the interactions between the target compounds and the amino acid residues of the Glycogen synthase kinase-3β. The docking studies were done using auto dock between computationally designed 2,5-disubstituted 1, 3, 4-oxadiazole derivatives and Glycogen synthase kinase-3beta (GSK-3β) protein. The Calculated free energy of binding and estimated inhibition constants (Ki) were remarkable when compared with the standard GSK-3 inhibitors. It is calculated by the Lamarckian Genetic Algorithm (LGA). These values & the proposed interactions suggested that the 2, 5-disubstituted-1, 3, 4-oxadiazole derivatives are excellent inhibitors of GSK-3β.
Shriram S. Purohit* and V.P. Veerapur
Department of Pharmaceutical Chemistry, S.E.T.’s College of Pharmacy, S.R. Nagar, Dharwad-580 002, Karnataka, India
23 July, 2012
03 September, 2012
29 October, 2012