Lai Shang-Hai, Li Wei, Yao Jun-Hua, Han Bing-Jie, Jiang Guang-Bin, Zhang Cheng, Zeng Chuan-Chuan, Liu Yun-Jun
School of Pharmacy, Guangdong Pharmaceutical University, Guangzhou 510006, PR China.
Instrumentation Analysis and Research Center, Sun Yat-Sen University, Guangzhou 510275, PR China.
J Photochem Photobiol B. 2016 May;158:39-48. doi: 10.1016/j.jphotobiol.2016.02.015. Epub 2016 Feb 27.
Four new ruthenium(II) polypyridyl complexes Ru(dmb)2(dqtbt)2 (1) (dqtbt=12-(2,3-diphenyl-quinoxalin-6-yl)-4,5,10,13-tetraazabenzo[b]triphenylene, dmb=4,4'-dimethyl-2,2'-bipyridine), Ru(bpy)2(dqtbt)2 (2) (bpy=2,2'-bipyridine), Ru(phen)2(dqtbt)2 (3) (phen=1,10-phenanthroline) and Ru(dmp)2(dqtbt)2 (4) (dmp=2,9-dimethyl-1,10-phenanthroline) were synthesized and characterized. The cytotoxicity in vitro of the complexes was evaluated against human BEL-7402, A549, HeLa, HepG-2 and MG-63 cancer cell lines. These complexes are sensitive to BEL-7402 cells, the IC50 values are 4.9±0.5, 4.6±0.4, 7.7±1.8 and 1.9±0.3μM toward BEL-7402 cells. The complexes can increase the levels of reactive oxygen species and induce the decrease of mitochondrial membrane potential. Morphological and comet assay studies show that the complexes can effectively induce apoptosis in BEL-7402 cells. Complexes 1-4 inhibit the cell growth at G0/G1 phase in BEL-7402 cell line. The complexes can downregulate the expression of Bcl-2 and Bcl-x proteins and upregulate the levels of Bid protein in BEL-7402 cells. The results show that the complexes induce BEL-7402 cell apoptosis through a ROS-mediated mitochondrial dysfunction pathway. In addition, the complexes show strong protein-binding affinities.
合成并表征了四种新型钌（II）多吡啶配合物Ru(dmb)2(dqtbt)2（1）（dqtbt = 12-(2,3-二苯基喹喔啉-6-基)-4,5,10,13-四氮杂苯并[b]三苯撑，dmb = 4,4'-二甲基-2,2'-联吡啶）、Ru(bpy)2(dqtbt)2（2）（bpy = 2,2'-联吡啶）、Ru(phen)2(dqtbt)2（3）（phen = 1,10-菲咯啉）和Ru(dmp)2(dqtbt)2（4）（dmp = 2,9-二甲基-1,10-菲咯啉）。评估了这些配合物对人BEL-7402、A549、HeLa、HepG-2和MG-63癌细胞系的体外细胞毒性。这些配合物对BEL-7402细胞敏感，对BEL-7402细胞的IC50值分别为4.9±0.5、4.6±0.4、7.7±1.8和1.9±0.3μM。这些配合物可增加活性氧水平并诱导线粒体膜电位降低。形态学和彗星试验研究表明，这些配合物可有效诱导BEL-7402细胞凋亡。配合物1-4在BEL-7402细胞系的G0/G1期抑制细胞生长。这些配合物可下调BEL-7402细胞中Bcl-2和Bcl-x蛋白的表达，并上调Bid蛋白水平。结果表明，这些配合物通过ROS介导的线粒体功能障碍途径诱导BEL-7402细胞凋亡。此外，这些配合物表现出很强的蛋白质结合亲和力。
