Novel thiazole–thiadiazole as a potential anti-Alzheimer agent: synthesis and molecular interactions via an in silico study

This study aimed to synthesize and evaluate a series of thiazole-derived thiadiazole-based Schiff base derivatives (1–16) for their potential anti-Alzheimer and antioxidant activities, with a focus on identifying promising drug-like candidates. The synthesized compounds were structurally characterized using ¹H-NMR, ¹³C-NMR, and mass spectrometry. Their biological potential was assessed via in vitro anti-Alzheimer assays (AChE and BuChE inhibition) and DPPH-based antioxidant screening. Molecular docking was employed to predict binding interactions with relevant protein targets. Additionally, ADMET profiling was carried out to evaluate pharmacokinetic and toxicity parameters. Among the tested compounds, derivative 8, bearing a trifluoromethyl substitution, showed the most potent activity against Alzheimer-related enzymes, surpassing the standard drug donepezil. Derivatives 3, 7, and 12 also exhibited significant bioactivity. Docking studies confirmed strong binding affinities of the active compounds to key residues within the enzyme active sites. ADMET analysis indicated favorable drug-likeness and safety profiles. The synthesized Schiff-base derivatives, especially compound 8, demonstrated strong anti-Alzheimer and antioxidant activity. These findings suggest their potential as lead candidates for further development of multifunctional therapeutics targeting neurodegenerative disorders.