Hasanvand Zaman, Motahari Rasoul, Nadri Hamid, Moghimi Setareh, Foroumadi Roham, Ayati Adileh, Akbarzadeh Tahmineh, Bukhari Syed Nasir Abbas, Foroumadi Alireza
Department of Medicinal Chemistry, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran.
Department of Medicinal Chemistry, Faculty of Pharmacy and Pharmaceutical Sciences Research Center, Shahid Sadoughi University of Medical Sciences, Yazd, Iran.
Front Chem. 2022 Aug 9;10:882191. doi: 10.3389/fchem.2022.882191. eCollection 2022.
A novel multifunctional series of 3-aminobenzofuran derivatives were designed and synthesized as potent inhibitors of acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE). The target compounds were prepared a three-step reaction, starting from 2-hydroxy benzonitrile. anti-cholinesterase activity exhibited that most of the compounds had potent acetyl- and butyrylcholinesterase inhibitory activity. In particular, compound containing 2-fluorobenzyl moiety showed the best inhibitory activity. Furthermore, this compound showed activity on self- and AChE-induced Aβ-aggregation and MTT assay against PC12 cells. The kinetic study revealed that compound showed mixed-type inhibition on AChE. Based on these results, compound can be considered as a novel multifunctional structural unit against Alzheimer's disease.
设计并合成了一系列新型多功能3-氨基苯并呋喃衍生物，作为乙酰胆碱酯酶（AChE）和丁酰胆碱酯酶（BuChE）的强效抑制剂。目标化合物通过三步反应制备，起始原料为2-羟基苯甲腈。抗胆碱酯酶活性表明，大多数化合物具有强效的乙酰胆碱酯酶和丁酰胆碱酯酶抑制活性。特别是，含有2-氟苄基部分的化合物表现出最佳的抑制活性。此外，该化合物对自身诱导和AChE诱导的Aβ聚集具有活性，并对PC12细胞进行了MTT测定。动力学研究表明，该化合物对AChE表现出混合型抑制作用。基于这些结果，该化合物可被视为一种针对阿尔茨海默病的新型多功能结构单元。
