Biological and computational evaluation of novel benzofuranyl derivatives as acetylcholinesterase and butyrylcholinesterase inhibitors

Abstract

Aim: A highly efficient one-step method has been developed for the synthesis of benzofuranyl derivatives from 2-benzoylcyclohexane-1-carboxylic acid derivatives using chlorosulfonyl isocyanate. This novel method provides a practical, cost-effective and efficient approach. Materials & methods: The inhibitory effects of benzofuranyl derivatives on acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) enzymes were investigated. Ki values were determined to range from 0.009 to 0.61 μM for AChE and 0.28 to 1.60 μM for BChE. Molecular docking analysis provided insights into the interaction modes and binding patterns of these compounds with AChE and BChE. Conclusion: Kinetic findings of our study suggest that some of our compounds exhibited more effective low micromolar inhibition compared with the reference, and these derivatives could be used to design more powerful agents.

Summary points

• Highly effective one-pot synthesis of novel benzofuranyl derivatives.

• Inhibitory potentials and molecular docking of synthesized novel benzofuranyl derivatives were investigated.

• Kinetic studies were conducted for benzofuranyl derivatives with AChE and BChE.

• IC₅₀ and Ki values were determined with AChE and BChE.

• The inhibition types of the inhibitors were determined.

• The most effective inhibitors were identified as 2i for AChE and 2e for BChE.

Keywords: :

• acetylcholinesterase
• Alzheimer's disease
• benzofuranyl
• butyrylcholinesterase
• molecular modeling

Supplemental material

Supplemental data for this article can be accessed at https://doi.org/10.1080/17568919.2024.2342641

Financial disclosure

The authors have no other relevant affiliations or 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 apart from those disclosed.

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.

Ethical conduct of research

The authors state that they have obtained appropriate institutional review board approval or have followed the principles outlined in the Declaration of Helsinki for all human or animal experimental investigations.