What question did this study set out to answer?

This study aims to evaluate the acetylcholinesterase inhibitory activity of novel arensulfonylhydrazinoxamoyl amine derivatives.

May 25, 2026Open Access

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

Key Points

This study aims to evaluate the acetylcholinesterase inhibitory activity of novel arensulfonylhydrazinoxamoyl amine derivatives.
Compounds were synthesized and characterized using H NMR and MS analysis.
In vitro biological profiling was conducted, measuring AChE inhibition and cytotoxicity against cancer cell lines.
In silico molecular docking studies and ADME/T analysis assessed binding efficacy and drug-likeness.
Compound 2 exhibited AChE inhibitory activity with IC₅₀ of 6.51 μM, more potent than compound 1's IC₅₀ of 24.05 μM.
Compound 2 showed moderate cytotoxic activity with IC₅₀ of 811.5 μM against HepG2 cells, while both compounds had weak activity against MCF-7 cells.
Molecular docking indicated favorable binding within the active site of human AChE, with weak interaction with BACE1, supporting further structural optimization.

Abstract

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.

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