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

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 µM, while the reference (galantamine) had IC50 =1.85±0.12 µM. Compounds 9 (IC50 75.14±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.