AI Article Synopsis

  • Researchers created a series of coumarin-pyridine compounds as potential multi-functional drugs for Alzheimer's disease (AD) treatment.
  • These compounds demonstrated strong inhibition of acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE), with some outperforming the standard drug donepezil.
  • The most effective compound not only inhibited key enzymes but also protected nerve cells from toxic effects and reduced harmful protein aggregation, indicating it could be a promising candidate for AD therapy.

Article Abstract

In this research, a series of coumarin-based scaffolds linked to pyridine derivatives a flexible aliphatic linkage were synthesized and assessed as multifunctional anti-AD agents. All the compounds showed acceptable acetylcholinesterase (AChE) inhibition activity in the nanomolar range (IC = 2-144 nM) and remarkable butyrylcholinesterase (BuChE) inhibition property (IC = 9-123 nM) compared to donepezil as the standard drug (IC = 14 and 275 nM, respectively). Compound as the best AChE inhibitor (IC = 2 nM) showed acceptable BuChE inhibition activity (IC = 24 nM), 100 times more active than the standard drug. Compound could also significantly protect PC12 and SH-SY5Y cells against HO-induced cell death and amyloid toxicity, respectively, superior to the standard drugs. It could interestingly reduce β-amyloid self and AChE-induced aggregation, more potent than the standard drug. All the results suggest that compound could be considered as a promising multi-target-directed ligand (MTDL) against AD.

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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9280334PMC
http://dx.doi.org/10.3389/fchem.2022.895483DOI Listing

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