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

Abstract

Aim: Design and synthesis of a series of hydrazone–sulfonate hybrids, 5a–r. Methodology: The inhibitory properties of the synthesized compounds against acetylcholinesterase and butyrylcholinesterase were evaluated using donepezil as the reference standard. Results & conclusion: Compound 5e was identified as the most potent inhibitor of acetylcholinesterase (IC₅₀ = 9.30 μM), and compound 5i 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.

Keywords::

• Alzheimer’s
• cholinesterase
• hydrazone–sulfonate
• molecular docking
• toxicological bioassays

Supplementary data

To view the supplementary data that accompany this paper please visit the journal website at: www.tandfonline.com/doi/suppl/10.4155/fmc-2023-0238

Financial disclosure

The authors have no financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending or royalties.

Competing interests disclosure

The authors have no competing interests or relevant affiliations with any organization or entity with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending or royalties.

Writing disclosure

No writing assistance was utilized in the production of this manuscript.