Rastegari_2018_Bioorg.Chem_83_391

Alzheimer's disease (AD) is a well-known neurodegenerative disorder affecting millions of old people worldwide and the corresponding epidemiological data highlights the significance of the disease. As AD is a multifactorial illness, various single-target directed drugs that have reached clinical trials have failed. Therefore, various factors associated with outset of AD have been considered in targeted drug discovery and development. In this work, a wide range of 1,2,3-triazole-chromenone carboxamides were designed, synthesized, and evaluated for their cholinesterase inhibitory activity. Among them, N-(1-benzylpiperidin-4-yl)-7-((1-(3,4-dimethylbenzyl)-1H-1,2,3-triazol-4-yl)metho xy)-2-oxo-2H-chromene-3-carboxamide (11b) showed the best acetylcholinesterase inhibitory activity (IC50=1.80microM), however, it was inactive toward butyrylcholinesterase. It should be noted that compound 11b was evaluated for its BACE1 inhibitory activity and calculated IC50=21.13microM confirmed desired inhibitory activity. Also, this compound revealed satisfactory neuroprotective effect against H2O2-induced cell death in PC12 neurons at 50microM as well as metal chelating ability toward Fe(2+), Cu(2+), and Zn(2+) ions.