Novel Coumarin-Pyridine Hybrids as Potent Multi-Target Directed Ligands Aiming at Symptoms of Alzheimer's Disease

Creative Commons License

Babaei E., Kucukkilinc T. T., Jalili-Baleh L., Nadri H., Oz E., Forootanfar H., ...Daha Fazla

FRONTIERS IN CHEMISTRY, cilt.10, 2022 (SCI-Expanded) identifier identifier identifier

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 10
  • Basım Tarihi: 2022
  • Doi Numarası: 10.3389/fchem.2022.895483
  • Dergi Adı: FRONTIERS IN CHEMISTRY
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus, Directory of Open Access Journals
  • Anahtar Kelimeler: Alzheimer's disease, cholinesterase inhibitors, coumarin derivatives, neurodegenerative diseases, docking study, ACETYLCHOLINESTERASE INHIBITORS, DERIVATIVES, DESIGN, TACRINE, DISCOVERY, DOCKING, AGGREGATION, MOIETY, DRUGS
  • Hacettepe Üniversitesi Adresli: Evet

Özet

In this research, a series of coumarin-based scaffolds linked to pyridine derivatives via 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 (IC50 = 2-144 nM) and remarkable butyrylcholinesterase (BuChE) inhibition property (IC50 = 9-123 nM) compared to donepezil as the standard drug (IC50 = 14 and 275 nM, respectively). Compound 3f as the best AChE inhibitor (IC50 = 2 nM) showed acceptable BuChE inhibition activity (IC50 = 24 nM), 100 times more active than the standard drug. Compound 3f could also significantly protect PC12 and SH-SY5Y cells against H2O2-induced cell death and amyloid toxicity, respectively, superior to the standard drugs. It could interestingly reduce beta-amyloid self and AChE-induced aggregation, more potent than the standard drug. All the results suggest that compound 3f could be considered as a promising multi-target-directed ligand (MTDL) against AD.