Thiazolidine-2,4-dione framework containing spiropyrrolidine-oxindole and 1,2,3-triazole scaffold: synthesis, in vitro a-amylase inhibition and in silico studies

In an attempt to develop novel a-amylase inhibitors, a series of 2,4-thiazolidinedione fused spiropyrrolidineoxindole and 1,2,3-triazole scaffolds were designed, synthesized via a multi-component approach and characterized using IR, H-1 NMR, C-13 NMR and DEPT based spectral studies. The exact structure of 9a was confirmed using single-crystal X-ray diffraction studies. The presence of various non-covalent interactions in the molecular structure of 9a was explored using Hirshfeld surface and PARST analysis. All of the synthesized compounds were assessed for in vitro a-amylase inhibition using acarbose as a positive standard. Compound 9b depicted maximum inhibition; 88.05 +/- 2.51%, 76.65 +/- 2.19% and 68.57 +/- 1.96% inhibition at 50, 25 and 12.5 mg mL(-1), respectively, relative to standard drug acarbose (77.96%, 71.17% and 67.25%, at 50, 25 and 12.5 mg mL(-1) concentration). In silico docking simulations were used to investigate the binding of the compounds within the binding pocket of a-amylase (PDB ID: 7TAA). Molecular dynamic simulations revealed the stability of the docked ligand-protein complexes.