Synthesis and anti-diabetic activity evaluation of phosphonates containing thiazolidinedione moiety

Abstract

A sequence of substituted phosphonates containing the thiazolidinedione moiety was synthesized with good yields. The structures of all the synthesized compounds were confirmed by NMR (31P, 1H and 13C) and IR spectroscopy, mass spectrometry and C, H, N elemental analyses. In silico molecular docking study was also carried out to evaluate their interaction and binding modes on ligands against human PPAR γ protein for their anti-diabetic activity. From the docking results, it was determined that the compounds (Z)-dimethyl 5-(3-nitrobenzylidene)−2,4-dioxothiazolidin-3-ylphosphonate (7a), (Z)-dimethyl 5-(3-chloro-4-fluorobenzylidene)−2,4-dioxothiazolidin-3-ylphosphonate (7f), (Z)-dimethyl 5-(2,4-dichlorobenzylidene)−2,4-dioxothiazolidin-3-ylphosphonate (7e) and (Z)-dimethyl 5-((5-methoxypyridin-2-yl)methylene)−2,4-dioxothiazolidin-3-ylphosphonate (7j) have shown better binding energies (−7.8, −7.6, −7.5 and −7.6 Kcal/mol) with the target gene, PPAR γ than the reference drug, Rosiglitazone (−7.4 Kcal/mol). In vitro anti-diabetic activity of the title compounds was also screened by standard α-amylase inhibition assay. Some of the tested compounds proved to possess promising activity when compared with the reference drug.