1. Novel Coumarin-Pyridine Hybrids as Potent Multi-Target Directed Ligands Aiming at Symptoms of Alzheimer's Disease.
- Author
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Babaei E, Küçükkılınç TT, Jalili-Baleh L, Nadri H, Öz E, Forootanfar H, Hosseinzadeh E, Akbari T, Ardestani MS, Firoozpour L, Foroumadi A, Sharifzadeh M, Mirjalili BBF, and Khoobi M
- 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 (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 H2 O2 -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., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The handling editor MS declared a shared affiliation with the authors EH, SM, MS, MK at the time of review., (Copyright © 2022 Babaei, Küçükkılınç, Jalili-Baleh, Nadri, Öz, Forootanfar, Hosseinzadeh, Akbari, Ardestani, Firoozpour, Foroumadi, Sharifzadeh, Mirjalili and Khoobi.)- Published
- 2022
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