Ruthenium complexes are expected to be new opportunities for the development of antitumor agents. Herein, four ruthenium polypyridyl complexes ([Ru(bpy)₂(CAPIP)](ClO₄)₂ (Ru(II)-1, bpy = 2,2′-bipyridine; CAPIP = (E)-2-(2-(furan-2-yl)vinyl)-1H-imidazo[4,5-f][1,10]phenanthroline), [Ru(phen)₂(CA-PIP)](ClO₄)₂ (Ru(II)-2, phen = 1,10-phenanthroline), [Ru(dmb)₂(CAPIP)](ClO₄)₂ (Ru(II)-3, dmb = 4,4′-dimethyl-2,2′-bipyridine), [Ru(dmb)₂(ETPIP)](ClO₄)₂ (Ru(II)-4, ETPIP = 2-(4-(thiophen-2-ylethynyl)phenyl)-1H-imidazo[4,5-f][1,10]phen-anthroline)) have been investigated as mitochondria-targeted antitumor metallodrugs. DNA binding studies indicated that target Ru(II) complexes interacts with CT DNA (calf thymus DNA) by an intercalative mode. Cytotoxicity assay results demonstrate that Ru(II) complexes show high cytotoxicity against A549 cells with low IC₅₀ value of 23.6 ± 2.3, 20.1 ± 1.9, 22.7 ± 1.8 and 18.4 ± 2.3 μM, respectively. Flow cytometry and morphological analysis revealed that these Ru(II) complexes can induce apoptosis in A549 cells. Intracellular reactive oxygen species (ROS) and mitochondrial membrane potential were also investigated by ImageXpress Micro XLS system. The experimental results indicate that the reactive oxygen species in A549 cells increased significantly and mitochondrial membrane potential decreased obviously. In addition, colocalization studies shown these complexes could get to the cytoplasm through the cell membrane and accumulate in the mitochondria. Furthermore, Ru(II) complexes can effectively induces cell cycle arrest at the S phase in A549 cells. Finally, cell invasion assay and quantitative studies were also performed to investigate the mechanism of this process. All in together, this study suggested that these Ru(II) complexes could induce apoptosis in A549 cells through cell cycle arrest and ROS-mediated mitochondrial dysfunction pathway.

钌配合物有望成为开发抗肿瘤药物的新机会。在这里，四个钌多吡啶基络合物（[Ru（bpy）₂（CAPIP）]（ClO ₄）₂（Ru（II）-1，bpy = 2,2'-bipyridine; CAPIP =（E）-2-（2- （呋喃-2-基）乙烯基）-1 H-咪唑并[4,5- f ] [1,10]菲咯啉），[Ru（phen）₂（CA-PIP）]（ClO ₄）₂（Ru（II ）-2，phen = 1,10-菲咯啉），[Ru（dmb ）₂（CAPIP）]（ClO ₄）₂（Ru（II）-3，dmb = 4,4'-dimethyldimethyl，2,2'-联吡啶），[Ru（dmb）₂（ETPIP）]（ClO ₄）₂（Ru（II）-4，ETPIP = 2-（4-（噻吩-2-基乙炔基）苯基）-1 H-咪唑并[4,5- f ] [1,10] phen-anthroline））已作为靶向线粒体的抗肿瘤金属药物进行了研究。DNA结合研究表明目标Ru（II）配合物通过插入模式与CT DNA（小牛胸腺DNA）相互作用。细胞毒性测定结果表明，Ru（II）配合物对低IC _50的A549细胞显示出高细胞毒性分别为23.6±2.3、20.1±1.9、22.7±1.8和18.4±2.3μM。流式细胞仪和形态分析表明，这些Ru（II）复合物可以诱导A549细胞凋亡。还使用ImageXpress Micro XLS系统研究了细胞内活性氧（ROS）和线粒体膜电位。实验结果表明，A549细胞中的活性氧显着增加，线粒体膜电位明显降低。此外，共定位研究表明，这些复合物可以通过细胞膜到达细胞质并堆积在线粒体中。此外，Ru（II）复合物可以有效诱导A549细胞中S期的细胞周期停滞。最后，还进行了细胞侵袭测定和定量研究以研究该过程的机制。总之，这项研究表明，这些Ru（II）配合物可以通过细胞周期停滞和ROS介导的线粒体功能障碍途径诱导A549细胞凋亡。