Aminothiazole Hybrids: Synthesis, In vitro Anticholinesterase Activity, and Binding Insights through Molecular Docking

Introduction: Aminothiazole is an important moiety exhibiting various biological properties, including antioxidant, bacteriostatic, antibiotic, anticonvulsant, anti-HIV, cytotoxic, antifungal, anti-inflammatory and neuroprotective activities. Materials and Methods: Here, we aimed to synthesise aminothiazole derivatives bearing an oxadiazole moiety and determine their inhibitory activity against the Acetylcholinesterase (AChE) enzyme. The antioxidant activity of all molecules was evaluated using the DPPH radical scavenging method. Results: Among all derivatives, compound 3b emerged as a potential candidate, exhibiting AChE inhibitory and antioxidant activity with IC₅₀ values of 3.55 μM and 2.17 μM, respectively. Discussion: In the molecular docking analysis, the best docking score was observed for the most active compound, 3b, which also showed strong in-vitro inhibition. Conclusion: The synthesised compound (3b) can be considered a potential lead for the further development of new compounds against Alzheimer’s disease.