Erdogan Orhan, IlkayDeniz, F. Sezer SenolSalmas, Ramin EkhteiariIrmak, SuleAcar, Ozden OzgunTurgut, Gurbet CelikSen, AlaattinZbancioc, Ana-MariaLuca, Simon VladSkalicka-Woźniak, KrystynaSkiba, AdriannaTataringa, Gabriela2024-05-152024-05-1520221612-1872https://doi.org/10.1002/cbdv.202200315https://hdl.handle.net/20.500.12573/2120Series 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.enginfo:eu-repo/semantics/closedAccessAlzheimer’s diseasecholinesterase inhibitioncoumarinmolecular modelingSH-SY5Ybiological activitysynthetic methodsarticle1912111