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Profiling donepezil template into multipotent hybrids with antioxidant properties.

Eva Mezeiova1,2, Katarina Spilovska1,2,3, Eugenie Nepovimova1,4,3

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Summary

New Alzheimer's treatments explore multi-target directed ligands (MTDLs) by modifying acetylcholinesterase inhibitors (AChEIs). This approach enhances antioxidant properties to combat Alzheimer's disease progression.

Keywords:
AcetylcholinesteraseAlzheimer’s diseasedonepezilmulti-target directed ligandsoxidative stress

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Area of Science:

  • Neuroscience and Pharmacology
  • Medicinal Chemistry

Background:

  • Alzheimer's disease (AD) is a severe neurodegenerative disorder primarily affecting the elderly.
  • Current treatments, including acetylcholinesterase inhibitors (AChEIs) and memantine, offer only short-term cognitive stabilization for up to two years.
  • Limitations of current therapies necessitate novel approaches to manage AD onset and progression.

Purpose of the Study:

  • To review emerging strategies for Alzheimer's disease therapy.
  • To focus on the development of multi-target directed ligands (MTDLs) based on the donepezil scaffold.
  • To explore MTDLs that combine anti-cholinesterase activity with enhanced antioxidant potential.

Main Methods:

  • Comprehensive literature survey.
  • Analysis of structurally modified donepezil derivatives.
  • Evaluation of multi-target directed ligands (MTDLs) for combined therapeutic effects.

Main Results:

  • Donepezil template has been successfully modified into numerous MTDLs.
  • These MTDLs retain significant anti-cholinesterase activity.
  • The modified ligands exhibit escalated antioxidant potential, a critical factor in AD pathogenesis.

Conclusions:

  • Multi-target directed ligands (MTDLs) represent a promising therapeutic strategy for Alzheimer's disease.
  • Modifying acetylcholinesterase inhibitors (AChEIs) like donepezil to include antioxidant properties offers a broader biological profile.
  • This dual-action approach holds potential for more effective management of AD onset and progression.