Synthesis, DFT, ADMET and molecular docking studies of thiazole derived thiazolidinone-based chalcone derivatives: alzheimer's disease current therapies

Future Med Chem. 2024 Dec 4:1-9. doi: 10.1080/17568919.2024.2421158. Online ahead of print.

Abstract

Aim: Nitrogen and sulfur-containing compounds are the core components utilized for synthesis of different heterocyclic moieties.

Methods & results: In this research, a series of new analogues containing thiazolidinone have been synthesized (1-20) in order to evaluate their activity against acetylcholinesterase and butyrylcholinesterase. Potent analogues were further subjected for molecular docking in order to study their protein-ligand interactions. The highly active analogues were also subjected for DFT, which confirmed the binding properties, electrical properties, and nature with the targeted enzyme. ADMET analysis also confirms the druglikeness properties of the synthesized series.

Conclusion: Analog 5 (IC50 = 1.2 ± 0.1 µM and 1.8 ± 0.2 µM) exhibit excellent inhibition in comparison with the standard drug donepezil in view of inhibiting Alzheimer's disease.

Keywords: AChE; BuChE; Synthesis; thiazole; thiazolidinone & chalcone.