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

Erdoğan Orhan I., Şenol Deniz F. S., Salmas R. E., Irmak S., Acar O. O., Turgut G. C., ...Daha Fazla

CHEMISTRY & BIODIVERSITY, cilt.19, 2022 (SCI-Expanded) identifier identifier identifier

  • 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.