Synthesis of Thioacetamide-Thiazoles as Anticholinesterase and Antioxidant Agents against Alzheimer’s Disease

Objective: synthesize thioacetamide-thiazole as key pharmacophore possessing acetylcholinesterase (AChE) inhibitory activity. Methods: Thirteen compounds (IIIa–IIIm) were synthesized by preparing differently substituted aminothiazoles and subsequently evaluated for AChE inhibitory and antioxidant activity. Results and Discussion: Compound (IIIk) (IC50 = 1.99 µM) exhibits promising AChE inhibitory activity amongvarious derivatives of the series. The antioxidant potential of synthesized compounds were determined by DPPH assay (IC50 = 1.10 to 15.45 µM). Compound (IIIk) exhibited the utmost antioxidant activity with IC50 = 1.10 µM. Further molecular docking, drug-likeness, and ADMET predictions of all synthesized compounds were also assessed with computational methods. The results unequivocally supported the in vitro studies of all derivatives by displaying good docking score with binding pocket of PDB4EY7. Conclusions: The study concluded that compound (IIIk) emerged as potential lead compound as AChE inhibitor for the development of new compounds as anti-Alzheimer’s candidates.