Saeedi_2020_Chem.Biodivers__

A novel series of hybrid arylisoxazole-chromenone carboxamides were designed, synthesized, and evaluated for their cholinesterase (ChE) inhibitory activity based on the modified Ellman's method. Among synthesized compounds, 5-(3-nitrophenyl)-N-(4-((2-oxo-2H-chromen-7-yl)oxy)phenyl)isoxazole-3-carboxamide (11h) depicted the most acetylcholinesterase (AChE) inhibitory activity (IC50 = 1.23 microM) and 5-(3-chlorophenyl)-N-(4-((2-oxo-2H-chromen-7-yl)oxy)phenyl)isoxazole-3-carboxamid e (11e) was found to be the most potent butyrylcholinesterase (BChE) inhibitor (IC50 = 9.71 microM). Compound 11h was further investigated for its BACE1 inhibitory activity as well as neuroprotectivity and metal chelating ability as important factors involved in onset and progress of Alzheimer's disease. It could inhibit BACE1 by 48.46% at 50 microM. Also, it showed 6.4% protection at 25 microM and satisfactory chelating ability toward Zn2+, Fe2+, and Cu2+ ions. Also, docking studies of compounds 11h and 11e confirmed desired interactions with those amino acid residues of the AChE and BChE, respectively.