Design and Synthesis of Novel Arylisoxazole‐Chromenone Carboxamides: Investigation of Biological Activities Associated with Alzheimer's Disease

• DOI: 10.1002/cbdv.201900746
• Publication Date: 2020-03-10T10:51:00Z
• Authors: Mina Saeedi; Arezoo Rastegari; Roshanak Hariri; Seyedeh Sara Mirf...; Mohammad Mahdavi; Najmeh Edraki; Omidreza Firuzi; Tahmineh Akbarzadeh
• Keywords: Oxazole; Carboxamide; Butyrylcholinesterase; Docking (animal); Cholinesterase; Lead compound

Abstract 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‐2 H ‐1‐benzopyran‐7‐yl)oxy]phenyl}‐1,2‐oxazole‐3‐carboxamide depicted most acetylcholinesterase (AChE) (IC 50 =1.23 μ m ) 5‐(3‐chlorophenyl)‐ was found to be potent butyrylcholinesterase (BChE) inhibitor =9.71 ). 5‐(3‐Nitrophenyl)‐ further investigated its BACE1 as well neuroprotectivity metal chelating ability important factors involved in onset progress Alzheimer's disease. It could inhibit by 48.46 % at . also showed 6.4 protection 25 satisfactory toward Zn 2+ , Fe Cu ions. Docking studies confirmed desired interactions with those amino acid residues AChE BChE, respectively.