Synthesis of (Z)-2-((2-(Benzylideneamino)ethyl)Amino)-3-Methylquinoxaline-6-Sulfonyl Azide Derivatives and Their Acetylcholinesterase and Butyryl Cholinesterase Inhibitory Activities

Abstract

Aims: This study synthesized  a series of (Z)-2-((2-(benzylideneamino)ethyl)amino)-3-methylquinoxaline-6-sulfonyl azide derivatives and evaluated their inhibitory activities against acetylcholinesterase (AChE) and butyrylcholinesterase (BChE). Methods: The derivatives were prepared by reacting 2-((2-aminoethyl)amino)-3-methylquinoxaline-6-sulfonyl azide with substituted aromatic aldehydes in glacial acetic acid under reflux conditions. The synthesized  compounds were characterized  using infrared and nuclear magnetic resonance spectroscopy. Their AChE and BChE inhibitory activities were determined spectrophotometrically using acetylthiocholine and butyrylcholine chloride as substrates, with eserine as the reference compound. Results: All tested derivatives showed inhibitory activity against both enzymes. Compound 1g showed the lowest AChE IC₅₀ value (10.8 ± 0.01 µM), followed by compound 1f (18.9 ± 0.01 µM). Against BChE, compound 1g showed the lowest IC₅₀ value (13.6 ± 0.03 µM), followed by compound 1e (16.9 ± 0.03 µM) and compound 1b (18.5 ± 0.03 µM). The observed activities varied across the substituted Schiff base derivatives, indicating that structural substitution influenced cholinesterase inhibition. The assay results also showed lower IC₅₀ values for the tested derivatives than for eserine under the reported conditions. Conclusion: The synthesized  quinoxaline sulfonyl azide Schiff bases demonstrated in vitro inhibitory activity against AChE and BChE. The results support further investigation of these derivatives, particularly compound 1g, as chemical scaffolds for the development and optimisation of cholinesterase inhibitors.