Universitas Indonesia Conferences, Asian Federation for Pharmaceutical Sciences (AFPS) 2019

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Molecular Docking Analysis and Optimization of Pharmacophore-Based Virtual Screening Pyrolidine Amide Derivative Compounds as DPP-4 Inhibitors
Ronaldo Heris, Arry Yanuar, Widya Dwi Aryati

Last modified: 2019-07-20


Background : One type of drug used in the treatment of diabetes mellitus is the DPP-4 inhibitor. Some studies have developed DPP-4 inhibitor drugs using pyrrolidine amide derivative compounds with the results of IC50 values, but there is no interactions have been found between pyrrolidine amide and DPP-4 derivative compounds and pharmacophore features for virtual screening for drug candidates.

Objective : The purpose of this study is to find the results of molecular docking analysis between DPP-4 compounds and pyrrolidine amide derivatives, and obtain the pharmacophore feature of the pyrrolidine amide derivatives compounds to be used in pharmacophore-based virtual screening.

Methods : In this study, molecular docking analysis of the pyrrolidine amide derivatives compound was carried out using the AutoDock, then the docked compounds were used as training set for pharmacophore-based virtual screening optimization using a database from the Database of Useful Decoys site: Enhanced on the Ligand Scout.

Results : The result of the molecular docking of 5T4B macromolecules using 248 compounds has found 86 compounds that have the potential as DPP-4 inhibitors. The compound has binding energy lower than -8.00 kcal and interacts with a triad catalytic site consisting of S1 (Ser630, Asn710, and His740), S2 (Glu205 and Glu206) and some compounds interact with S3 (Val207, Ser209, Phe357, and Arg358). The results of the optimization of virtual screening are an AUC value of the ROC curve of 51% and EF of 5.7.

Conclusion : The results of this study indicate that the pyrrolidine amide derivative compound has potential as a DPP-4 inhibitor, but the pharmacophore feature that can be used to find DPP-4 inhibitor candidate compounds have not found yet.


Key Words : diabetes mellitus, DPP-4 inhibitors, molecular docking, pharmacophore-based virtual screening, pyrolidine amide derivatives