Type 2 diabetes mellitus (T2DM) remains a major global health burden, and despite the availability of several oral hypoglycaemic agents, issues such as adverse effects, loss of efficacy and drug resistance persist. Dipeptidyl peptidase-4 (DPP4) is a validated therapeutic target in glucose homeostasis, and both synthetic inhibitors and natural compounds such as curcumin have shown DPP4-modulating potential. Glibenclamide, a second-generation sulfonylurea, is widely used but associated with hypoglycaemia and weight gain. Rationally designing a glibenclamide–curcumin conjugate may enhance efficacy and safety by combining complementary mechanisms. The crystal structure of human DPP4 (PDB ID: 5Y7H) was retrieved from the Protein Data Bank and prepared using AutoDock Tools by removing water molecules and co-crystallized ligands, adding non-polar hydrogens and Kollman charges, and saving structures in pdbqt format. Curcumin, glibenclamide and their conjugate were sketched in ChemDraw, energy-minimized in Chem3D (MM2), converted to 3D, and prepared with Gasteiger charges and defined rotatable bonds. Molecular docking was performed using AutoDock Vina in PyRx. Binding energies and interaction profiles were analysed using PyMOL and Biovia Discovery Studio. Docking scores against DPP4 were −7.2 kJ/mol for curcumin, −7.8 kJ/mol for glibenclamide and −8.5 kJ/mol for the glibenclamide–curcumin conjugate, indicating superior affinity of the conjugate. Key interactions included multiple conventional hydrogen bonds, π–π stacking, π–anion and hydrophobic contacts with critical residues such as Glu205, Tyr662, Phe357, Arg125, Arg356 and Arg669, supporting enhanced complex stability. The glibenclamide–curcumin conjugate demonstrated stronger predicted binding to DPP4 than either parent molecule alone, suggesting a promising dual-acting scaffold for anti-diabetic drug development. These in silico findings warrant further in vitro and in vivo validation.
Keywords: Curcumin, Glibenclamide, DPP4 inhibitor, Molecular docking, Diabetes mellitus
How to cite this article: Mahesh DM, Abhay JS, Amit KA, Molecular Docking Study Of Glibenclamide, Curcumin And Glibenclamide-Curcumin Conjugate Against Dpp-4 Protein. Int J Drug Deliv Technol. 2026;16(2s): 170-176; DOI: 10.25258/ijddt.16.170-176