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

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 (P-31, H-1 and C-13) 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 gamma 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 gamma than th reference drug, Rosiglitazone (-7.4 Kcal/mol). In vitro anti-diabetic activity of the title compounds was also screened by standard alpha-amylase inhibition assay. Some of the tested compounds proved to possess promising activity when compared with the reference drug. [GRAPHICS] .