Evaluation of Anti-Alzheimer Activity of Synthetic Coumarins by Combination of in Vitro and in Silico Approaches
Chemistry and Biodiversity, cilt.19, sa.12, 2022 (SCI-Expanded, Scopus)
- Yayın Türü: Makale / Tam Makale
- Cilt numarası: 19 Sayı: 12
- Basım Tarihi: 2022
- Doi Numarası: 10.1002/cbdv.202200315
- Dergi Adı: Chemistry and Biodiversity
- Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus, Aquatic Science & Fisheries Abstracts (ASFA), CAB Abstracts, Chemical Abstracts Core, EMBASE, MEDLINE, Veterinary Science Database
- Anahtar Kelimeler: Alzheimer's disease, cholinesterase inhibition, coumarin, molecular modeling, SH-SY5Y, biological activity, synthetic methods
- Gazi Üniversitesi Adresli: Evet
Özet
© 2022 Wiley-VHCA AG, Zurich, Switzerland.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.