DOI: 10.36347/sajp

Pages: 26-37

A series of novel benzisoxazole containing thiazolidinediones were designed, docked with PPAR-γ protein leading to identification of a highly potent PPAR-γ agonist, compound S7. Based on molecular docking studies and lipinski’s rule of five, nine analogues out of 12 were synthesized and characterized by FT-IR, 1H-NMR and Mass spectra. Anti-diabetic activity of nine analogues was evaluated in alloxan (70 mg/kg, i.v.)-induced diabetes in mice [single-dose one day study]. The molecular docking and the pharmacological studies revealed that the distances between the acidic group and the linker, when a ligand was complexed with PPAR-γ protein, are important for the potent activity. The acidic head part of S7 makes intensive hydrophobic interaction with the PPAR-γ protein resulting in potent activity.