Design, Synthesis and Biological Evaluation of (Z)-N,N-dibenzyl-3-oxo-2-((2-((1 phenylethylidene) amino)ethyl)amino)-3,4-dihydroquinoxaline-6-sulfonamide Derivatives

Abstract

Aims: The aim is to synthesize a range of chemical derivatives and thoroughly evaluate their potential biological activities. This process will involve designing and executing synthetic pathways to obtain the desired compounds, followed by in-depth biological assays to assess properties such as acetylthiocholine and butyryl choline chloride. These evaluations will help determine their efficacy, safety and mechanism of action, providing insights into their potential use in pharmaceuticals or other medical applications. Methods: The substituted (Z)-N,N-dibenzyl-3-oxo-2-((2-((1-phenylethylidene)amino)ethyl)amino)-3,4-dihydroquinoxaline-6-sulfonamides were synthesized through the reaction of 2-((2-aminoethyl)amino)-N,N-dibenzyl-3-oxo-1,2,3,4-tetrahydroquinoxaline-6-sulfonamide with various substituted aromatic aldehydes. The resulting compounds were characterized using nuclear magnetic resonance (NMR) spectroscopy. Acetylcholinesterase and butyrylcholinesterase inhibitory activities were assessed by spectrophotometric analysis using acetylthiocholine and butyrylcholine chloride as substrates. Results: Compounds 1a-1h exhibited potent inhibition of acetylcholinesterase, with IC50 values ranging from 25.5 ± 0.02 µg/mL to 50.2 ± 0.07 µg/mL, compared with Eserine, which had an IC50 value of 40.0 ± 0.01 µg/mL. Similarly, all the compounds (1a-1h) demonstrated significant inhibition of butyrylcholinesterase, with IC50 values ranging from 20.5 ± 0.03 µg/mL to 43.6 ± 0.03 µg/mL, whereas Eserine had an IC50 value of 48.3 ± 0.03 µg/mL. Conclusion: The remarkable acetylcholinesterase and butyrylcholinesterase inhibitory activities of these compounds suggest their potential as candidates for the development of selective inhibitors of these enzymes.