Hydrazone–Sulfonate Hybrids as Potential Cholinesterase Inhibitors: Design, Synthesis and Molecular Modeling Simulation

Abstract

<b>Aim:</b> Design and synthesis of a series of hydrazone-sulfonate hybrids, <b>5a-r</b>. <b>Methodology:</b> The inhibitory properties of the synthesized compounds against acetylcholinesterase and butyrylcholinesterase were evaluated using donepezil as the reference standard. <b>Results & conclusion:</b> Compound <b>5e</b> was identified as the most potent inhibitor of acetylcholinesterase (IC₅₀ = 9.30 μM), and compound <b>5i</b> was the most potent inhibitor of butyrylcholinesterase (IC₅₀ = 11.82 μM). To confirm the safety of the most potent hits at the used doses, toxicological bioassays were conducted. Molecular docking was performed and the tested derivatives were found to fit well in the active sites of both enzymes. This study provides valuable insights into the potential of hydrazone-sulfonate hybrids as drug candidates.