Discovery of novel isoflavone derivatives as AChE/BuChE dual-targeted inhibitors: synthesis, biological evaluation and molecular modelling.
Discovery of novel isoflavone derivatives as AChE/BuChE dual-targeted inhibitors: synthesis, biological evaluation and molecular modelling.
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DOI：
10.1080/14756366.2017.1347163
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发表时间：
2017-12
影响因子：
5.6
通讯作者：
Wu S
中科院分区：
文献类型：
--
作者：
Feng B;Li X;Xia J;Wu S
AChE和BuChE是发现抗阿尔茨海默病药物的药物靶点，而这两个靶点的双重抑制似乎更有效。在这项研究中，我们合成了一系列新的化合物G的基础上，我们击中高通量筛选，然后在体外AChE和BuChE生物测定测试其活性。大多数的乙酰胆碱酯酶和乙酰胆碱酯酶的抑制剂的衍生物显示中度。其中，化合物16被鉴定为有效的AChE/BuChE双靶向抑制剂（IC 50：AChE为4.60 μM; BuChE为5.92 μM）。分子模拟研究表明，化合物16可能具有更好的药代动力学性质，例如吸收、血脑屏障穿透和CYP 2D 6结合。综上所述，我们的研究已经确定化合物16是治疗阿尔茨海默病的优秀先导化合物。
AChE and BuChE are druggable targets for the discovery of anti-Alzheimer’s disease drugs, while dual-inhibition of these two targets seems to be more effective. In this study, we synthesised a series of novel isoflavone derivatives based on our hit compound G from in silico high-throughput screening and then tested their activities by in vitro AChE and BuChE bioassays. Most of the isoflavone derivatives displayed moderate inhibition against both AChE and BuChE. Among them, compound 16 was identified as a potent AChE/BuChE dual-targeted inhibitor (IC50: 4.60 μM for AChE; 5.92 μM for BuChE). Molecular modelling study indicated compound 16 may possess better pharmacokinetic properties, e.g. absorption, blood–brain barrier penetration and CYP2D6 binding. Taken together, our study has identified compound 16 as an excellent lead compound for the treatment of Alzheimer’s disease.
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影响因子：
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作者：
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通讯作者：
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