Synthesis, crystal structures, α-glucosidase and α-amylase inhibition, DFT and molecular docking investigations of two thiazolidine-2,4-dione derivatives

In this work, two thiazolidine-2,4-dione derivatives 3 and 4 have been synthesized and characterized through infrared (IR), nuclear magnetic resonance (¹H/¹³C NMR), mass spectrometry (ESI-MS) and single-crystal X-ray diffraction (XRD). The optimized geometries, the vibrational frequencies, the frontier molecular orbital (HOMO-LUMO) energies and thermodynamic properties of the two molecules 3 and 4 were investigated using Density Functional Theory (DFT) calculation at the B3LYP/6-31++G(d,p) level of theory. Further, 3 and 4 were tested in vitro for their anti-diabetic activity through the inhibition of α-glucosidase and α-amylase enzymes. Binding interactions of 3 and 4 with α-glucosidase and α-amylase binding sites were emphasized by the analysis of molecular docking outputs. The results showed that the two compounds have low binding energies and good affinity toward the active site residues. Thus, they may be considered as good inhibitors of α-glucosidase and α-amylase enzymes.