Orhan_2022_Chem.Biodivers__

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 microM, while the reference (galanthamine) had IC50= 1.85 +/- 0.12 microM. Compounds 9 (IC5075.14 +/- 1.82 microM), 13 (IC50=16.14 +/- 0.43 microM), were determined to be stronger BChE inhibitors than the reference galanthamine (IC50= 93.53 +/- 2.23 microM). The IC50 value of compound 16 for BChE inhibition (IC50=126.56 +/- 11.96 microM) 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 line. Our data indicate that they could be considered for further evaluation as new anti-Alzheimer drug candidates.