In:
Frontiers in Chemistry, Frontiers Media SA, Vol. 10 ( 2022-6-30)
Abstract:
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 (IC 50 = 2–144 nM) and remarkable butyrylcholinesterase (BuChE) inhibition property (IC 50 = 9–123 nM) compared to donepezil as the standard drug (IC 50 = 14 and 275 nM, respectively). Compound 3f as the best AChE inhibitor (IC 50 = 2 nM) showed acceptable BuChE inhibition activity (IC 50 = 24 nM), 100 times more active than the standard drug. Compound 3f could also significantly protect PC12 and SH-SY5Y cells against H 2 O 2 -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 3f could be considered as a promising multi-target-directed ligand (MTDL) against AD.
Type of Medium:
Online Resource
ISSN:
2296-2646
DOI:
10.3389/fchem.2022.895483
DOI:
10.3389/fchem.2022.895483.s001
Language:
Unknown
Publisher:
Frontiers Media SA
Publication Date:
2022
detail.hit.zdb_id:
2711776-5