Pharmacophore Mapping, Docking and Three Dimensional QSAR Analysis of [(S)- γ -(Arylamino) Prolyl] Thiazolidine Compounds As A Potent and Stable DPP-IV Inhibitors

Novel DPP-IV (Dipeptidyl peptidase-IV) inhibitors were designed based on a previously describedseries diabetes. Despite years of continual efforts, diabetes is still one of the most dangerous diseases inthe world. The enzyme which increases the level of glucose in the body is DPP-IV. Inhibition of DPPIVis currently explored as a novel therapy for treatment of type 2 diabetes. In view of that we haveattempt to design a novel DP-IV inhibiting agents through molecular modeling. Essentialpharmacophoric feature were identified using ligand Scout. The common pharmacophoric featureswere identified by Pharmacophore mapping, three pharmacophoric sites were found to be hydrogenbond acceptor and other two were hydrogen bond donor. Pharmacophoric feature is shown by colorcoding. In addition docking study was also performed using Molegro 5.0, to establish theoretical drugreceptor interaction between ligands and DPP-IV enzyme. It was found that all the ligands formed ahydrogen bond interaction with His 740 of DPP-IV enzyme. The unbound His 740 is essential for theinhibition of DPP-IV enzyme The multi parameter 3D QSAR models have also generated, describedrelationship of DPP-IV inhibitory activity and physiochemical parameters, result can be used forstructure optimization. Among several 3D QSAR model, two models with good statistical values wereselected. Activity of model 1 and model 2 with good correlation coefficient was (0.6357 and 0.8470)and internal predictivity was (0.9744 and 0.6741). The results are promising and can be used to designnovel DPP-IV inhibiting agents.