Synthesis, in vitro and in vivo Antidiabetic Activity of N-Substituted Thiazolidinedione Derivatives

A series of novel, N-substituted thiazolidinediones (TZD) were synthesized, characterized and evaluated for antidiabetic activity. Of the 22 designed molecules, 12 compounds were successfully synthesized and structurally validated by IR, 1H NMR, 13C NMR and mass spectra. The absence of the N-H peak in the NMR spectrum verified successful condensation at the nitrogen of the thiazolidinedione ring. In vitro toxicity was assessed via the MTT assay on C2C12 cell lines, with most of compounds exhibiting IC50 values above 250 µM/mL, indicating low cytotoxicity. Glucose uptake studies evaluated the efficacy of these derivatives, revealing that compounds B-TZD-11 and B-TZD-13 significantly enhanced glucose absorption, comparable to standard antidiabetic agents like pioglitazone. In vivo evaluated the anti-hyperglycemic activity of B-TZD-11 and B-TZD-13 in high fat diet-streptozotocin-induced diabetic model. Both compounds significantly reduced fasting blood glucose, improved insulin sensitivity (HOMA-IR) and favourably modulated lipid profiles. B-TZD-13 showed superior efficacy, with the greatest glucose-lowering effect and improved glucose tolerance in oral glucose tolerance test (OGTT). Body weight analysis confirmed weight loss in the diabetic rats, mitigated by treatments. N-substituted thiazolidinedione derivatives bearing lipophilic moieties exhibited promising antidiabetic activity.