Synthesis and molecular docking studies of some 4-phthalimidobenzenesulfonamide derivatives as acetylcholinesterase and butyrylcholinesterase inhibitors

Abstract

A series of 4-phthalimidobenzenesulfonamide derivatives were designed, synthesized and evaluated for the inhibitory activities against acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE). Structures of the title compounds were confirmed by spectral and elemental analyses. The cholinesterase (ChE) inhibitory activity studies were carried out using Ellman’s colorimetric method. The biological activity results revealed that all of the title compounds (except for compound 8) displayed high selectivity against AChE. Among the tested compounds, compound 7 was found to be the most potent against AChE (IC₅₀= 1.35 ± 0.08 μM), while compound 3 exhibited the highest inhibition against BuChE (IC₅₀= 13.41 ± 0.62 μM). Molecular docking studies of the most active compound 7 in AChE showed that this compound can interact with both the catalytic active site (CAS) and the peripheral anionic site (PAS) of AChE.

Keywords:

• Acetylcholinesterase inhibitor
• butyrylcholinesterase inhibitor
• molecular docking
• phthalimide
• sulfonamide

Acknowledgements

The authors would like to thank the Pharmaceutical Sciences Research Center (FABAL) at Ege University Faculty of Pharmacy for spectral analyses of the compounds.

Disclosure statement

The authors declare no conflicts of interests.

Funding

This study was supported by research grants from Ege University (Project Number: 12/Ecz/016).