State Key Laboratory for Chemistry and Molecular Engineering of Medicinal Resources, School of Chemistry and Pharmacy, Guangxi Normal University, 15 Yucai Road, Guilin 541004, PR China.
State Key Laboratory for Chemistry and Molecular Engineering of Medicinal Resources, School of Chemistry and Pharmacy, Guangxi Normal University, 15 Yucai Road, Guilin 541004, PR China.
Eur J Med Chem. 2019 Feb 1;163:333-343. doi: 10.1016/j.ejmech.2018.11.047. Epub 2018 Nov 23.
Two gold(III) complexes of isoquinoline derivatives: [Au(L)Cl] (Au1) and [Au(L)Cl] (Au2) have been prepared and characterized. Au1 and Au2 exhibited greater cytotoxicity than their corresponding ligands and cisplatin against T-24 cells. Both complexes arrested cell cycle at S-phase by upregulation of p53, p27, and p21, and downregulation of cyclin A and cyclin E. The depolarization of the mitochondrial membrane potential, generation of ROS, and stimulated Ca release activated the caspase cascade and ultimately caused apoptosis by increasing the levels of Bax and Bak, and decreasing the levels of Bcl-2 and Bcl-xl. Cell apoptosis was achieved via mitochondria mediated pathways. The in vivo studies of Au1 and Au2 demonstrated that they were safer than cisplatin and could effectively inhibit tumor growth.
两种异喹啉衍生物的金（III）配合物：[Au(L)Cl]（Au1）和[Au(L)Cl]（Au2）已经被制备和表征。Au1 和 Au2 对 T-24 细胞的细胞毒性大于其相应的配体和顺铂。两种配合物通过上调 p53、p27 和 p21，下调细胞周期蛋白 A 和细胞周期蛋白 E，将细胞周期阻滞在 S 期。线粒体膜电位去极化、ROS 的产生和 Ca 释放的刺激激活了 caspase 级联反应，最终通过增加 Bax 和 Bak 的水平，降低 Bcl-2 和 Bcl-xl 的水平，导致细胞凋亡。细胞凋亡是通过线粒体介导的途径实现的。Au1 和 Au2 的体内研究表明，它们比顺铂更安全，能有效抑制肿瘤生长。
