A series of berberine-thiophenyl hybrids were designed, synthesised, and evaluated as inhibitors of acetylcholinesterase (AChE), butyrylcholinesterase (BuChE) and β-amyloid (Aβ) aggregation and as antioxidants. Among these hybrids, compounds 4f and 4i, berberine linked with o-methylthiophenyl and o-chlorothiophenyl by a 2-carbon spacer, were observed to be potent inhibitors of AChE, with IC50 values of 0.077 and 0.042 μM, respectively. Of the tested compounds, 4i was also the most potent inhibitor of BuChE, with an IC50 value of 0.662 μM. Kinetic studies and molecular modelling simulations of the AChE-inhibitor complex indicated that a mixed-competitive binding mode existed for these berberine derivatives. The biological studies also demonstrated that these hybrids displayed interesting activities, including Aβ aggregation inhibition and antioxidant properties.

译文

:设计,合成并评估了一系列小ber碱-硫代苯基杂化物,作为乙酰胆碱酯酶(AChE),丁酰胆碱酯酶(BuChE)和β-淀粉样蛋白(Aβ)聚集的抑制剂和抗氧化剂。在这些杂种中,观察到化合物4f和4i(通过2碳间隔基与邻甲基硫代苯基和邻氯硫代苯基连接的小ber碱)是有效的AChE抑制剂,IC50值分别为0.077和0.042μM。在测试的化合物中,4i也是BuChE的最强抑制剂,IC50值为0.662μM。 AChE-抑制剂复合物的动力学研究和分子建模模拟表明,这些小碱衍生物存在混合竞争结合模式。生物学研究还表明,这些杂种表现出有趣的活性,包括抑制Aβ聚集和抗氧化性能。

+1
+2
100研值 100研值 ¥99课程
检索文献一次
下载文献一次

去下载>

成功解锁2个技能,为你点赞

《SCI写作十大必备语法》
解决你的SCI语法难题!

技能熟练度+1

视频课《玩转文献检索》
让你成为检索达人!

恭喜完成新手挑战

手机微信扫一扫,添加好友领取

免费领《Endnote文献管理工具+教程》

微信扫码, 免费领取

手机登录

获取验证码
登录