Key Laboratory of Natural Medicine and Immuno-Engineering of Henan Province, Henan University Jinming Campus, Kaifeng, Henan, China.
Institute of Behavior and Psychology, Henan University Jimming Campus, Kaifeng, Henan, China.
Chem Biol Drug Des. 2019 Apr;93(4):617-627. doi: 10.1111/cbdd.13459. Epub 2019 Jan 11.
A series of novel quinoxaline derivatives were synthesized and evaluated for their antiproliferative activity in three human cancer cell lines. Compound 12 exhibited the most potent antiproliferative activity with IC in the range of 0.19-0.51 μM. The compound inhibited tubulin polymerization and disrupted the microtubule network, leading to G2/M phase arrest. Furthermore, compound 12 induced ROS production and malfunction of mitochondrial membrane potential. Compound 12 led to cancer cells apoptosis in a dose-dependent manner. Western blot analysis showed that compound 12 induced up-regulation of p21 and affected the expression of cell cycle-related proteins. The binding mode was also probed by molecular docking.
一系列新型的喹喔啉衍生物被合成出来，并在三种人类癌细胞系中评估其抗增殖活性。化合物 12 表现出最强的抗增殖活性，IC 在 0.19-0.51 μM 的范围内。该化合物抑制微管蛋白聚合并破坏微管网络，导致 G2/M 期阻滞。此外，化合物 12 诱导 ROS 产生和线粒体膜电位功能障碍。化合物 12 以剂量依赖的方式诱导癌细胞凋亡。Western blot 分析表明，化合物 12 诱导 p21 的上调，并影响细胞周期相关蛋白的表达。分子对接也探测了结合模式。
