A New Class of Benzo[ b]thiophene-chalcones as Cholinesterase Inhibitors: Synthesis, Biological Evaluation, Molecular Docking and ADME Studies

Molecules. 2024 Aug 7;29(16):3748. doi: 10.3390/molecules29163748.

Abstract

In this study, heterocyclic compounds containing a benzothiophene scaffold were designed and synthetized, and their inhibitory activity against cholinesterases (ChE) and the viability of SH-SY5Y cells have been evaluated. Benzothiophenes 4a-4i and benzothiophene-chalcone hybrids 5a-5i were tested against both acetylcholinesterase (AChE) and butyrylcholinesterase (BChE), revealing interesting structure-activity relationships. In general, benzothiophene-chalcone hybrids from series 5 proved to be better inhibitors of both enzymes, with compound 5f being the best AChE inhibitor (IC50 = 62.10 μM) and compound 5h being the best BChE inhibitor (IC50 = 24.35 μM), the last one having an IC50 similar to that of galantamine (IC50 = 28.08 μM), the reference compound. The in silico ADME profile of the compounds was also studied. Molecular docking calculations were carried out to analyze the best binding scores and to elucidate enzyme-inhibitors' interactions.

Keywords: benzothiophenes; cholinesterase inhibitors; heterocycles.

MeSH terms

  • Acetylcholinesterase* / chemistry
  • Acetylcholinesterase* / metabolism
  • Butyrylcholinesterase* / chemistry
  • Butyrylcholinesterase* / metabolism
  • Cell Line, Tumor
  • Chalcones* / chemical synthesis
  • Chalcones* / chemistry
  • Chalcones* / pharmacology
  • Cholinesterase Inhibitors* / chemical synthesis
  • Cholinesterase Inhibitors* / chemistry
  • Cholinesterase Inhibitors* / pharmacology
  • Humans
  • Molecular Docking Simulation*
  • Molecular Structure
  • Structure-Activity Relationship
  • Thiophenes* / chemical synthesis
  • Thiophenes* / chemistry
  • Thiophenes* / pharmacology

Substances

  • Cholinesterase Inhibitors
  • Thiophenes
  • Chalcones
  • Butyrylcholinesterase
  • Acetylcholinesterase
  • benzothiophene

Grants and funding

This research received no external funding.