SYNTHESIS, MOLECULAR DOCKING STUDIES AND BIOLOGICAL EVALUATION OF 5-[4-(SUBSTITUTED) BENZYLIDENE OR BENZYL] THIAZOLIDINE-2, 4-DIONE WITH THEIR ORAL HYPOGLYCEMIC ACTIVITY

Abstract

A new series of 5-[4-(substituted) benzylidene or benzyl] thiazolidine-2, 4-dione (TZDs) have been synthesized using economical synthetic routes. The aim of the synthesis based on modification of linker region and effector region of rosiglitazone. Among these newly synthesized compounds, based on their docking results, some compounds were selected for study of oral hypoglycemic activity on fructose induced hyperglycemia in Wistar rats. The results of selected compounds shows that, 5-[4-(2-amino-5-ethoxypyridine) sulphonyl benzylidene] thiazolidine-2, 4-dione and 5-[4-(2-amino-5-ethoxypyridine) ethoxy benzyl] thiazolidine-2, 4-dione have appreciable blood glucose-lowering effect compared to that of the reference drug, pioglitazone. Out of these two compounds, 5- [4-(2-amino-5-ethoxypyridine)ethoxy benzyl] thiazolidine-2, 4-dione shows better hydrogen bond interaction with amino acid residues of peroxisome proliferator activated receptor-gamma (PPARY) and also shows better oral hypoglycemic activity in this series.