Synthesis and in vitro/in silico evaluation studies of arensulfonylhydrazinoxamoyl amine and amino acid derivatives as preliminary acetylcholinesterase inhibitors

H NMR, and MS analyses, confirming their structures and high purity. The biological profiles of the compounds were evaluated using combined in vitro and in silico approaches. Both derivatives exhibited measurable acetylcholinesterase (AChE) inhibitory activity, with compound 2 showing greater potency (IC₅₀ = 6.51 ± 0.33 µM) than compound 1 (IC₅₀ = 24.05 ± 1.29 µM), although both less active than the reference inhibitor donepezil. Cytotoxicity evaluation revealed weak activity against MCF-7 breast cancer cells and moderate activity against HepG2 liver cancer cells, with compound 2 again demonstrating superior activity (IC₅₀ = 811.5 ± 32.2 µM). Molecular docking studies supported favourable binding of both compounds within the active gorge of human AChE (PDB: 4EY7), while interactions with BACE1 were weak and non-specific. In silico ADME/T analysis suggested acceptable drug-likeness with no violations of Lipinski's rule, although the high polarity of compound 1 indicated low oral absorption. PASS predictions did not indicate Alzheimer-specific activity but suggested general potential protease- and kinase-related inhibition. Overall, these compounds represent preliminary scaffolds with modest AChE inhibition and limited cytotoxicity, requiring structural optimisation for further therapeutic development.