Molecular Docking Of Dual PPAR Alpha/Gama Agonist For Type 2 Diabetes Structure Based Drug Design For Selective Cyclooxygenase-2(COX 2) Inhibitor
Year: 2025
Type: article
Abstract: Type 2 Diabetes Mellitus (T2DM) is a multifactorial metabolic disorder characterized by insulin resistance, dyslipidemia, and chronic inflammation. The nuclear receptors PPAR-α and PPAR-γ regulate lipid and glucose metabolism and are prominent therapeutic targets. This study investigates Aleglitazar, a known dual PPAR-α/γ agonist, and its structural derivatives for potential multi-target activity, including COX-2 inhibition. A structure-based drug design (SBDD) approach was employed using molecular docking techniques via AutoDock Vina to simulate ligand binding within the active sites of PPAR-α, PPAR-γ, and COX-2. Five compounds, including the parent Aleglitazar and four functionalized analogues (–COONa, –CH₃, –NH₂, –OH), were computationally optimized and docked against selected target receptors (PDB IDs: 2P54 and 3CS8). Compound 2 (–COONa) exhibited the most favorable binding energy and pose stability for both PPAR isoforms. The study also explored whether COX-2 inhibitory pharmacophores could be integrated without disrupting PPAR binding. Visual analysis using PyMOL confirmed significant receptor interactions, particularly via hydrogen bonding and hydrophobic contacts. The research demonstrates the utility of in silico docking as a cost-effective and predictive tool in the early phases of drug discovery, with implications for the development of dual or triple-target agents with improved efficacy and reduced side effects.
DOI: 10.53555/69cmgy22
Authors: Pranjal Kale, Aarti Nandwana, Neha Chouhan, Sikha Nagle, Archana Tiwari, P.K. Dubey
Language: English
Subfield: Computational Theory and Mathematics
Field: Computer Science
Domain: Physical Sciences
Open Access status: diamond
OpenAlex ID: W4413766098