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.

Graphical Abstract

Keywords:

• Phosphonates
• thiazolidinedione
• molecular docking study
• α-amylase inhibition assay

Acknowledgment

Authors thanks to Dr. C. Naga Raju, Department of Chemistry, S. V. University, Tirupati for his constant support; Lila Impex pharmaceuticals, Vijayawada and HCU, Hyderabad for providing spectral data.