1School of Pharmaceutical Sciences, Chhatrapati Shahu Ji Maharaj University, Kanpur, Uttar Pradesh 208024, India
Email: amritasingh@csjmu.ac.in, ajaykumar@csjmu.ac.in, shashikmishra@csjmu.ac.in
2Institute of pharmacy, Bundelkhand University, Jhansi, India
Email: drpankajniranjan@gmail.com
Diabetes mellitus (DM) is a lifelong metabolic disorder characterized by chronic hyperglycemia resulting from defects in insulin secretion, insulin action, or both. The global prevalence of DM is increasing at a frightening rate to over 783 million cases projected by 2045. Type 2 diabetes mellitus (T2DM), the most common form, is a companion of insulin resistance, glucose uptake defect, and impaired glycogen metabolism. Glycogen synthase kinase-3 (GSK-3) is a serine/threonine protein kinase involved in the central regulation of insulin action by its phosphorylation and inhibition of glycogen synthase and, thus, in hyperglycemia. Inhibition of GSK-3 has been viewed as a therapeutic strategy to amplify insulin sensitivity and offer better Glycemic control.
The current research focuses on the synthesis and characterization of new imidazolidine-2,4-dione derivatives as prospective GSK-3 inhibitors. Two-step synthesis pathway was chosen starting from benzoyl chloride analogues which were treated with p-hydroxybenzaldehyde to give intermediate products, followed by condensation with hydantoin derivatives. Synthesized compounds were characterized through thin layer chromatography (TLC), melting point measurement, and spectroscopic analysis (IR, NMR, and mass spectrometry). Molecular docking experiments performed by AutoDock Vina were performed to ascertain binding capacity to GSK-3β. Some of the compounds possessed favorable binding scores, such as the o-phenyl, p-phenyl, and m-triethylammonium substituted compound, which shows great promise as GSK-3 inhibitors.
These findings point to imidazolidine-2,4-dione derivatives with selective aromatic and heterocyclic substitutions as good lead compounds for anti-diabetic drug research and development. Further studies in vitro and in vivo would be required to ascertain their pharmacological activity and safety profiles.
Keywords: Diabetes mellitus, GSK-3 inhibitors, Imidazolidine-2,4-dione, Hydantoin derivatives, Docking studies, Anti-diabetic drug design.
How to cite this article: Singh A, Kumar A, Niranjan PS, Misra SK. Design, Synthesis, and In Silico Evaluation of Novel Imidazolidine-2,4-dione Derivatives as Selective GSK-3β Inhibitors. Int J Drug Deliv Technol. 2026;16(8s): 188-203; DOI: 10.25258/ijddt.16.8s.30
Source of support: Nil.
Conflict of interest: Nil.