Orhan, Ilkay ErdoganDeniz, F. Sezer SenolSalmas, Ramin EkhteiariIrmak, SuleAcar, Ozden OzgunTurgut, Gurbet CelikTataringa, GabrielaErdogan Orhan, Ilkay2025-09-252025-09-2520221612-18721612-1880https://doi.org/10.1002/cbdv.202200315https://hdl.handle.net/20.500.12573/3795Luca, Simon Vlad/0000-0003-0904-0060; Skiba, Adrianna/0000-0001-6601-8295; Zbancioc, Ana Maria/0000-0002-3031-6829; Senol Deniz, Fatma Sezer/0000-0002-5850-9841;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.eninfo:eu-repo/semantics/closedAccessAlzheimer's DiseaseCholinesterase InhibitionCoumarinMolecular ModelingSH-SY5YBiological ActivitySynthetic MethodsArticle10.1002/cbdv.2022003152-s2.0-85143230188