发现新型含有 4-氧代喹啉部分的吡咯并[2,3-b]吡啶衍生物作为潜在的抗肿瘤抑制剂。
Discovery of novel pyrrolo[2,3-b]pyridine derivatives bearing 4-oxoquinoline moiety as potential antitumor inhibitor.
机构信息
School of Perfume and Aroma Technology, Shanghai Institute of Technology; Engineering Research Center of Perfume & Aroma and Cosmetics of Ministry of Education, Shanghai 201418, PR China.
Jiangxi Provincial Key Laboratory of Drug Design and Evaluation, School of Pharmacy, Jiangxi Science & Technology Normal University, Nanchang 330013, PR China; School of Optoelectronic Science and Engineering, University of Electronic Science and Technology of China (UESTC), Chengdu 610054, PR China.
出版信息
Bioorg Med Chem Lett. 2020 Jan 15;30(2):126848. doi: 10.1016/j.bmcl.2019.126848. Epub 2019 Dec 2.
A series of pyrrolo[2,3-b]pyridine derivatives bearing 4-oxoquinoline moiety were designed, synthesized and evaluated for the anti-proliferative on three cancer cell lines (A549, HepG2 and MCF-7) in vitro. Most of the compounds showed moderate to high potency. Some excellent compounds were tested for the inhibitory activity of c-Met kinase. Compound 34 (c-Met IC = 17 nM) was investigated the selectivity against Flt-3, c-Kit, VEGFR-2, ALK, PDGFR-β and RON. Structure-activity relationship studies indicated that hydrogen, fluorine atom, and mono-electron-withdrawing groups (mono-EWGs, such as R = F) on R, R and R, respectively, were beneficial for the anti-proliferative activities of the target compounds. Besides, we have took further study on the combined mode between compound 34 and c-Met kinase through molecular docking.
设计、合成了一系列含有 4-氧代喹啉部分的吡咯并[2,3-b]吡啶衍生物，并在体外评估了它们对三种癌细胞系（A549、HepG2 和 MCF-7）的增殖抑制活性。大多数化合物表现出中等至高的活性。一些优秀的化合物被测试了对 c-Met 激酶的抑制活性。化合物 34（c-Met IC = 17 nM）对 Flt-3、c-Kit、VEGFR-2、ALK、PDGFR-β 和 RON 的选择性进行了研究。构效关系研究表明，R、R 和 R 上的氢、氟原子和单吸电子基团（单吸电子基团，如 R = F）分别有利于目标化合物的增殖抑制活性。此外，我们还通过分子对接进一步研究了化合物 34 与 c-Met 激酶的结合模式。
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