Evaluation of Anti-Alzheimer Activity of Synthetic Coumarins by Combination of in Vitro and in Silico Approaches
CHEMISTRY & BIODIVERSITY, cilt.19, 2022 (SCI-Expanded)
- Yayın Türü: Makale / Tam Makale
- Cilt numarası: 19
- Basım Tarihi: 2022
- Doi Numarası: 10.1002/cbdv.202200315
- Dergi Adı: CHEMISTRY & 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, BIOLOGICAL EVALUATION, BUTYRYLCHOLINESTERASE, CHOLINESTERASE, MATRIX-METALLOPROTEINASE-9, INHIBITORS, DISCOVERY, PROTEIN, DESIGN
- Abdullah Gül Üniversitesi Adresli: Evet
Özet
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 mu M, while the reference (galantamine) had IC50=1.85 +/- 0.12 mu M. Compounds 9 (IC(50)75.14 +/- 1.82 mu M), 13 (IC50=16.14 +/- 0.43 mu M), were determined to be stronger BChE inhibitors than the reference galantamine (IC50=93.53 +/- 2.23 mu M). The IC50 value of compound 16 for BChE inhibition (IC50=126.56 +/- 11.96 mu M) 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.