3‐Aryl Coumarin Derivatives Bearing Aminoalkoxy Moiety as Multi‐Target‐Directed Ligands against Alzheimer's Disease
| Autor: | Seyed Esmaeil Sadat Ebrahimi, Alireza Foroumadi, Zahra Abdolahi, Beyza Ayazgök, Leili Jalili-Baleh, Tuba Tüylü Küçükkılınç, Helia Abdshahzadeh, Mehdi Khoobi, Setareh Moghimi, Mostafa Golshani, Hamid Forootanfar, Ismaeil Haririan, Hamid Nadri, Alieh Ameri, Iraj Saberi Kia |
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| Rok vydání: | 2019 |
| Předmět: |
Molecular model
Stereochemistry Apoptosis Bioengineering Ligands PC12 Cells 01 natural sciences Biochemistry Inhibitory Concentration 50 Structure-Activity Relationship chemistry.chemical_compound Alzheimer Disease Coumarins Catalytic Domain Animals Humans Moiety Molecular Biology Butyrylcholinesterase Cholinesterase Amyloid beta-Peptides Binding Sites biology 010405 organic chemistry Aryl Active site Hydrogen Peroxide General Chemistry General Medicine Coumarin Rats 0104 chemical sciences Molecular Docking Simulation Kinetics 010404 medicinal & biomolecular chemistry Neuroprotective Agents chemistry Acetylcholinesterase biology.protein Molecular Medicine Amine gas treating Cholinesterase Inhibitors |
| Zdroj: | Chemistry & Biodiversity. 16:e1800436 |
| ISSN: | 1612-1880 1612-1872 |
| DOI: | 10.1002/cbdv.201800436 |
| Popis: | Two series of novel coumarin derivatives, substituted at 3 and 7 positions with aminoalkoxy groups, are synthesized, characterized, and screened. The effect of amine substituents and the length of cross-linker are investigated in acetyl- and butyrylcholinesterase (AChE and BuChE) inhibition. Target compounds show moderate to potent inhibitory activities against AChE and BuChE. 3-(3,4-Dichlorophenyl)-7-[4-(diethylamino)butoxy]-2H-chromen-2-one (4y) is identified as the most potent compound against AChE (IC50 =0.27 μm). Kinetic and molecular modeling studies affirmed that compound 4y works in a mixed-type way and interacts simultaneously with the catalytic active site (CAS) and peripheral anionic site (PAS) of AChE. In addition, compound 4y blocks β-amyloid (Aβ) self-aggregation with a ratio of 44.11 % at 100 μm and significantly protects PC12 cells from H2 O2 -damage in a dose-dependent manner. |
| Databáze: | OpenAIRE |
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