恶唑
化学
甲酰胺
乙酰胆碱酯酶
丁酰胆碱酯酶
立体化学
对接(动物)
胆碱酯酶
螯合作用
铅化合物
阿切
酶
药理学
生物化学
体外
有机化学
护理部
医学
作者
Mina Saeedi,Arezoo Rastegari,Roshanak Hariri,Seyedeh Sara Mirfazli,Mohammad Mahdavi,Najmeh Edraki,Omidreza Firuzi,Tahmineh Akbarzadeh
标识
DOI:10.1002/cbdv.201900746
摘要
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 the most acetylcholinesterase (AChE) inhibitory activity (IC 50 =1.23 μ m ) and 5‐(3‐chlorophenyl)‐ N ‐{4‐[(2‐oxo‐2 H ‐1‐benzopyran‐7‐yl)oxy]phenyl}‐1,2‐oxazole‐3‐carboxamide was found to be the most potent butyrylcholinesterase (BChE) inhibitor (IC 50 =9.71 μ m ). 5‐(3‐Nitrophenyl)‐ N ‐{4‐[(2‐oxo‐2 H ‐1‐benzopyran‐7‐yl)oxy]phenyl}‐1,2‐oxazole‐3‐carboxamide 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 μ m . It also showed 6.4 % protection at 25 μ m and satisfactory chelating ability toward Zn 2+ , Fe 2+ , and Cu 2+ ions. Docking studies of 5‐(3‐nitrophenyl)‐ N ‐{4‐[(2‐oxo‐2 H ‐1‐benzopyran‐7‐yl)oxy]phenyl}‐1,2‐oxazole‐3‐carboxamide and 5‐(3‐chlorophenyl)‐ N ‐{4‐[(2‐oxo‐2 H ‐1‐benzopyran‐7‐yl)oxy]phenyl}‐1,2‐oxazole‐3‐carboxamide confirmed desired interactions with those amino acid residues of the AChE and BChE, respectively.
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