Synthesis, Computational Docking, and Enzyme Inhibition Profiles of Novel Thiazolidine-2,4-dione Derivatives

International Journal of Chemistry | Vol. 2, No. 12, December 2011 | pp. 116–123

DOI: 10.46882/2011/IJC/000039

Article Type: Original Research Paper

Title: Synthesis, Computational Docking, and Enzyme Inhibition Profiles of Novel Thiazolidine-2,4-dione Derivatives

Names of Authors: O. M. Kolawole¹, L. C. Nwosu¹*

Authors’ Affiliations:
¹Department of Chemistry, Obafemi Awolowo University, Ile-Ife, Nigeria.

Abstract: Thiazolidine-2,4-dione (TZD) rings are important pharmacophores used to manage type 2 diabetes mellitus due to their ability to activate peroxisome proliferator-activated receptor gamma (PPAR-gamma). In this work, five novel 5-benzylidene-thiazolidine-2,4-dione derivatives were synthesized via Knoevenagel condensation of TZD with various substituted benzaldehydes in the presence of piperidine catalysts. The chemical frameworks of the synthesized molecules were confirmed using elemental analysis, FT-IR, and ¹H-NMR spectroscopy. In vitro alpha-glucosidase enzyme inhibition assays revealed that compound 4c, bearing a p-nitro substituent, possessed the highest inhibitory potency, showing an IC50 value of 14.5 μM, compared to the acarbose clinical standard (IC50 = 38.2 μM). To investigate the binding orientations, in silico molecular docking simulations were run inside the catalytic site of alpha-glucosidase using AutoDock Vina. The docking models showed that the TZD carbonyl oxygen forms stable hydrogen bonds with Arg315 and Asp214 residues. The aromatic ring extensions fit well into the hydrophobic pocket, forming pi-pi stacking interactions with Phe178. These structural contacts stabilize the ligand-protein framework, supporting the low inhibition constants and highlighting these derivatives as promising antidiabetic drug candidates.

Keywords: Thiazolidine-2,4-dione; Knoevenagel condensation; Alpha-glucosidase; Enzyme inhibition; Molecular docking; Antidiabetic candidates

Manuscript Timeline: Received: May 05, 2011; Revised: June 18, 2011; Accepted: July 10, 2011; Published: December 04, 2011.

Citation: Kolawole, O. M., & Nwosu, L. C. (2011). Synthesis, Computational Docking, and Enzyme Inhibition Profiles of Novel Thiazolidine-2,4-dione Derivatives. International Journal of Chemistry, 2(12), 116–123.

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