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

Abstract

In the present study, a series of thiazolidine-2,4-diones derivatives (<b>3a-3e</b>) and (<b>4a-4e</b>) were synthesized and characterized by ¹H NMR, ¹³C NMR and ESI-MS spectrometry. All compounds were screened for their α-glucosidase and α-amylase inhibitory activities. <i>In vitro</i> biological investigations revealed that most of compounds were active against α-glucosidase with IC₅₀ values in the range of 43.85 ± 1.06 to 380.10 ± 1.02 µM, and α-amylase with IC₅₀ in the range of 18.19 ± 0.11 to 208.10 ± 1.80 µM. Some of the tested compounds were found to be more potent inhibitors than the clinical drug Acarbose (IC_{50glucosidase} = 97.12 ± 0.35 µM and IC_50amylase = 2.97 ± 0.004 μM). 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 α-glucosidase and α-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 α-amylase (PDB ID: 1B2Y) and α-glucosidase (PDB ID: 3W37)Communicated by Ramaswamy H. Sarma.