Abdpour_2021_Bioorg.Chem_110_104750

A new serise of 7-hydroxy-chromone derivatives bearing pyridine moiety were synthesized, and evaluated as multifunctional agents against Alzheimer's disease (AD). Most of the compounds were good AChE inhibitors (IC(50) = 9.8-0.71 microM) and showed remarkable BuChE inhibition activity (IC(50) = 1.9-0.006 microM) compared with donepezil as the standard drug (IC(50) = 0.023 and 3.4 microM). Compounds 14 and 10 showed the best inhibitory activity toward AChE (IC(50) = 0.71 microM) and BuChE (IC(50) = 0.006 microM), respectively. The ligand-protein docking simulations and kinetic studies revealed that compound 14 and 10 could bind effectively to the peripheral anionic binding site (PAS) of the AChE and BuChE through mixed-type inhibition. In addition, the most potent compounds showed acceptable neuroprotective activity on H(2)O(2)- and Abeta-induced .neurotoxicity in PC12 cells, more than standard drugs. The compounds could block effectively self- and AChE-induced Abeta aggregation. All the results suggest that compounds 14 and 10 could be considered as promising multi-target-directed ligands against AD.