In Silico Analysis of 2,4-Thiazolidinedione Derivatives as Potential Insulin Sensitizers for the Treatment of Diabetes Mellitus

This study explores the design and evaluation of 2,4-thiazolidinedione (TZD) compounds as potential antidiabetic candidate through in silico methods. A total of 22 TZD derivatives were virtually designed, assessed for synthetic accessibility, and analyzed for ADME properties using Maestro 24.3. Molecular docking studies against the PPARδ receptor (PDB ID: 5Y2O) identified B-TZD11 and B-TZD13 as the most promising candidates, exhibiting strong binding interactions. Toxicity predictions using Protox-III indicated moderate toxicity (Class 4), with some compounds showing nephrotoxicity and BBB penetration. The derivatives demonstrated favorable pharmacokinetic properties, including high oral absorption and metabolic stability. Computational studies indicate that these compounds may act as insulin sensitizers, but further biological testing is needed to assess their effectiveness and potential risks. This study supports the development of innovative antidiabetic agents with improved therapeutic benefits.