Department of Pharmacy Engineering, Tianjin University of Technology, Tianjin 300384, PR China.
College of Traditional Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin 300193, PR China.
Bioorg Med Chem Lett. 2019 Jun 1;29(11):1325-1329. doi: 10.1016/j.bmcl.2019.03.050. Epub 2019 Mar 30.
Dual binding site acetylcholinesterase (AChE) inhibitors and butyrylcholinesterase (BChE) inhibitors have recently emerged as two classes of new anti-Alzheimer agents to positively modify the disease's course. In this work, a new series of 4-N-phenylaminoquinolines was synthesized and evaluated for their abilities to inhibit AChE and BChE. Compound 11b showed significant inhibitory activities on AChE and BChE with IC values of 0.86 and 2.65 μM, respectively, a lot better than that of reference drug galanthamine. Furthermore, docking study showed that compound 11b interacted simultaneously not only with active and peripheral sites of AChE, but also with all five regions of BChE active site. These findings suggest that these derivatives could be regarded as promising starting points for further drug discovery developments.
双重结合位点乙酰胆碱酯酶（AChE）抑制剂和丁酰胆碱酯酶（BChE）抑制剂最近已成为两类新型抗阿尔茨海默病药物，可积极改善疾病进程。在这项工作中，合成了一系列新的 4-N-苯基氨基喹啉，并评估了它们抑制 AChE 和 BChE 的能力。化合物 11b 对 AChE 和 BChE 的抑制活性分别为 0.86 和 2.65 μM，明显优于参考药物加兰他敏。此外，对接研究表明，化合物 11b 不仅与 AChE 的活性和外周结合位点相互作用，而且与 BChE 活性位点的所有五个区域相互作用。这些发现表明，这些衍生物可以作为进一步药物发现开发的有前途的起点。
