Synthesis, alpha-glucosidase and alpha-amylase inhibitory activities, acute toxicity and molecular docking studies of thiazolidine-2,4-diones derivatives

In the present study, a series of thiazolidine-2,4-diones derivatives (3a-3e) and (4a-4e) were synthesized and characterized by H-1 NMR, C-13 NMR and ESI-MS spectrometry. All compounds were screened for their alpha-glucosidase and alpha-amylase inhibitory activities. In vitro biological investigations revealed that most of compounds were active against alpha-glucosidase with IC50 values in the range of 43.85 +/- 1.06 to 380.10 +/- 1.02 mu M, and alpha-amylase with IC50 in the range of 18.19 +/- 0.11 to 208.10 +/- 1.80 mu M. Some of the tested compounds were found to be more potent inhibitors than the clinical drug Acarbose (IC50glucosidase = 97.12 +/- 0.35 mu M and IC50amylase = 2.97 +/- 0.004 mu M). The lead compounds were evaluated for their acute toxicity on Swiss mice and found to be completely non-toxic with LD > 2000 mg/kg BW. Furthermore, the Structure-activity relationship (SAR) and the binding interactions of all compounds with the active site of alpha-glucosidase and alpha-amylase were confirmed through molecular docking and stabilizing energy calculations. This study has identified the inhibitory potential a new class of synthesized thiazolidine-2,4-diones in controlling both hyperglycemia and type 2 diabetes mellitus. Furthermore, the theoretical binding mode of the target molecules was evaluated by molecular docking studies against the 3D Crystal Structure of human pancreatic alpha-amylase (PDB ID: 1B2Y) and alpha-glucosidase (PDB ID: 3W37) Communicated by Ramaswamy H. Sarma