Design, synthesis, and antidiabetic evaluation of thiazolidinedione derivatives as potent PPAR-γ Agonists: Insights from molecular docking, MD simulations and invitro studies

A novel series of thiazolidinedione derivatives (D1-D30) were designed, synthesized, and characterized for potential anti-diabetic activity. Compounds D6, D8, and D24 emerged as promising candidates based on their structural attributes. These compounds were characterized using spectroscopic techniques. Molecular docking studies demonstrated their interactions with the Peroxisome Proliferator-Activated Receptor Gamma (PPAR-gamma), a target for anti-diabetic drugs. Molecular dynamics simulations validated the stability of these ligand-PPAR-gamma complexes. Additionally, the cytotoxicity of the compounds was evaluated using the MTT assay in L6 myoblast cell lines, a standard method to assess cell viability. The synthesized compounds were also tested for their in vitro glucose-uptake activity, revealing that D6, D8, and D24 exhibited significant glucose-uptake activity compared to the reference drug Pioglitazone. These findings suggest that these compounds have potential as effective antidiabetic agents.