Li Kun, Li Ying, Zhou Di, Fan Yinbo, Guo Hongye, Ma Tianyi, Wen Jiachen, Liu Dan, Zhao Linxiang
Key Laboratory of Structure-Based Drugs Design & Discovery of Ministry of Education, Shenyang Pharmaceutical University, Shenyang 110016, China.
School of Life Sciences and Biopharmaceutics, Shenyang Pharmaceutical University, Shenyang 110016, China.
Bioorg Med Chem. 2016 Apr 15;24(8):1889-97. doi: 10.1016/j.bmc.2016.03.016. Epub 2016 Mar 7.
In this work, a series of quinoline derivatives were designed and synthesized as antitumor agents. Most quinolines showed potent anti-proliferative activity against human prostatic cancer PC-3 cell line. Among which, 9d, 9f and 9g were the most effective compounds with GI50 values of 2.60, 2.81 and 1.29 μM, respectively. Structure-activity relationship analysis indicated that the secondary amine linked quinoline and pyridine ring played an important role in the anti-proliferative effects. Mechanistic studies revealed that 9g was a potential Pim-1 kinase inhibitor with abilities of cell cycle arrest and apoptosis induction. Considering of the increased activity of Pim-1 in prostate cancer, such compounds have potential to be developed as anti-prostate cancer agents.
在本研究中，设计并合成了一系列喹啉衍生物作为抗肿瘤药物。大多数喹啉对人前列腺癌PC-3细胞系显示出较强的抗增殖活性。其中，9d、9f和9g是最有效的化合物，其GI50值分别为2.60、2.81和1.29 μM。构效关系分析表明，连接喹啉和吡啶环的仲胺在抗增殖作用中起重要作用。机制研究表明，9g是一种潜在的Pim-1激酶抑制剂，具有细胞周期阻滞和诱导凋亡的能力。鉴于Pim-1在前列腺癌中的活性增加，这类化合物有潜力被开发为抗前列腺癌药物。
