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 (3a–3e) and (4a–4e) 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. In vitro 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

Keywords:

• Thiazolidine-2,4-diones
• α-amylase
• α-glucosidase
• SAR
• docking
• acute toxicity

Acknowledgements

The authors would like to acknowledge the UATRS-CNRST and Analysis and Characterization Platform ACP-FSR for ¹³C NMR, ¹H NMR, mass spectra and IR respectively.

Disclosure statement

The authors declare that they have no competing financial interests that could have appeared to influence the work reported in this paper.

Additional information

Funding

This work is supported by CNRST-Morocco, UM5R, and UM6P.