Ligand Based in-silico Study on Pyridopyrimidinedione Derivatives as Dipeptidyl Peptidase-IV Inhibitors
Piyush Ghode, Jain Sanmati Kumar · Indian Journal of Pharmaceutical Education and Research · 2017
Background: Type-2 diabetes mellitus can be effectively treated with dipeptidyl peptidase-IV inhibitors.Diverse classes of molecules have exhibited promising DPP-IV inhibition.Objective: In this perspective, 3D-QSAR and pharmacophore studies on a series of substituted pyridopyrimidinedione derivatives were performed to explore the structural requirements for effective DPP-IV inhibitory activity.Methods: 3D-QSAR was performed on 3D-QSAR module of Vlife molecular design suite (MDS) while two strategies were used for pharmacophore identification: MolSign module of MDS and Pharmagist.Results: The most significant 3D-QSAR models obtained from kNN and PLSR exhibited 79% and 77% of internal and 66% and 67% of external predictability respectively.The results from both kNN and PLSR models suggest the contribution of electronegative group with optimum bulk to be favourable for biological activity.Additional information about field point S_376 suggests a more bulky group to be favourable around S_376 at R1.The results from pharmacophore studies by both the strategies indicate the contribution of three hydrogen bond acceptors, one hydrogen bond donor and one aromatic feature for biological activity.Conclusion: Findings of the present study can be utilized for development of new lead compounds exhibiting promising DPP-IV inhibitory activity.