In silico identification of potential 2-thioxothiazolidin-4-one derivatives against peroxisome proliferator-activated receptor-gamma by molecular docking, MM-GBSA, molecular dynamic simulation, and toxicity studies
Mahendra Gowdru Srinivasa, Manohar Mahadev, Sudeep Darbhe Ghate, Shivakiran Alva, Vinay C. Sangamesh, B. C. Revanasiddappa · Journal of Biomolecular Structure and Dynamics · 2025
The metabolic disorder diabetes mellitus occurs when there is an inadequate level of insulin or excessive insulin resistance. There has been evidence that this pathogenesis has been approached via a different strategy. It activates homeostatic glucose and improves peripheral glucose utilization by targeting the PPAR-γ. In this regard, the present study aims to investigate 2-thioxothiazolidin-4-one derivatives (D1-15) as PPAR-γ regulators by computational approach followed by evaluation of physicochemical properties and ADMET profiles. The protein target PPAR-γ (PDB ID: 3DZY) was docked against 2-thioxothiazolidin-4-one derivatives using the glide suite. The results indicate the high binding affinity of compounds D7, D11 (−6.509 and −7.276 kcal/mol) and they were compared against standard drug rosiglitazone (−7.289 kcal/mol). MD simulation studies were also carried out at 150 ns to identify the key interactions in protein-ligand complexes in a dynamic environment not only to confirm our findings but to validate them as well. The findings indicated that certain designed compounds, namely D7 and D11, exhibited notable activity against PPAR-γ inhibitors, as evidenced by their favorable glide scores. The chosen derivatives of 2-thioxothiazolidin-4-one appear to hold promise as potential sources for advancing the development of antidiabetic agents targeting the PPAR-γ enzyme.