Evaluation of Anti‐Alzheimer Activity of Synthetic Coumarins by Combination of in Vitro and in Silico Approaches

Series of synthetic coumarin derivatives (1‐16) were tested against acetylcholinesterase (AChE) and butyrylcholinesterase (BChE), two enzymes linked to the pathology of Alzheimer's disease (AD). Compound 16 was the most active AChE inhibitor with IC50 32.23±2.91 μM, while the reference (galanta...

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Published in:Chemistry & biodiversity 2022-12, Vol.19 (12), p.e202200315-n/a
Main Authors: Erdogan Orhan, Ilkay, Deniz, F. Sezer Senol, Salmas, Ramin Ekhteiari, Irmak, Sule, Acar, Ozden Ozgun, Turgut, Gurbet Celik, Sen, Alaattin, Zbancioc, Ana‐Maria, Luca, Simon Vlad, Skiba, Adrianna, Skalicka‐Woźniak, Krystyna, Tataringa, Gabriela
Format: Article
Language:English
Subjects:
Acetylcholinesterase
Acetylcholinesterase - metabolism
Alzheimer Disease - drug therapy
Alzheimer's disease
Amino acids
Atomic interactions
Binding
biological activity
Butyrylcholinesterase - metabolism
Cell lines
cholinesterase inhibition
Cholinesterase Inhibitors - chemistry
Cholinesterase Inhibitors - pharmacology
Coumarin
Coumarins - chemistry
Coumarins - pharmacology
Drug development
Galantamine
Humans
Ligands
Molecular Docking Simulation
molecular modeling
Neuroblastoma
Neurodegenerative diseases
SH-SY5Y
Structure-Activity Relationship
synthetic methods
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Summary:Series of synthetic coumarin derivatives (1‐16) were tested against acetylcholinesterase (AChE) and butyrylcholinesterase (BChE), two enzymes linked to the pathology of Alzheimer's disease (AD). Compound 16 was the most active AChE inhibitor with IC50 32.23±2.91 μM, while the reference (galantamine) had IC50=1.85±0.12 μM. Compounds 9 (IC5075.14±1.82 μM), 13 (IC50=16.14±0.43 μM), were determined to be stronger BChE inhibitors than the reference galantamine (IC50=93.53±2.23 μM). The IC50 value of compound 16 for BChE inhibition (IC50=126.56±11.96 μM) was slightly higher than galantamine. The atomic interactions between the ligands and the key amino acids inside the binding cavities were simulated to determine their ligand‐binding positions and free energies. The three inhibitory coumarins (9, 13, 16) were next tested for their effects on the genes associated with AD using human neuroblastoma (SH‐SY5Y) cell lines. Our data indicate that they could be considered for further evaluation as new anti‐Alzheimer drug candidates.
ISSN:1612-1872
1612-1880
DOI:10.1002/cbdv.202200315