Two new Ru(II) complexes containing O, O-chelated ligands, Ru(dip)₂(SA) (Ru-1) and Ru(dmp)₂(SA) (Ru-2) (dip = 4,7-diphenyl-1,10-phenanthroline; dmp = 2,9-dimethyl-1,10-phenanthroline; SA = salicylate) were synthesized to evaluate their cytotoxicity in vitro. These complexes were found to exhibit moderate antitumor activity to different types of human cancers, including A549 (human lung carcinoma), MCF-7 (breast cancer), HeLa (human cervical cancer), and HepG2 (human hepatocellular carcinoma) cell lines, but displayed low toxicity to human normal cell lines BEAS-2B (immortalized human bronchial epithelial cells) when compared with that of cisplatin. Further studies revealed that these complexes could induce apoptosis in A549 cells, including activating caspase family proteins and poly (ADP-ribose) polymerase (PARP), reducing Bcl-2/Bax and Bcl-xl/Bad ratio, enhancing cellular reactive oxygen species (ROS) accumulation, triggering DNA damage, decreasing mitochondrial membrane potential (MMP), and leading cytochrome c release from mitochondria. Notably, complex Ru-1 showed low toxicity to developing zebrafish embryos. The obtained results suggest that these new synthetic complexes have the potential to be developed as low-toxicity agents for lung cancer treatment.

中文翻译：

---

带有O，O-螯合配体的Ru（II）络合物通过线粒体凋亡途径诱导A549细胞凋亡。

包含O，O螯合配体Ru（dip）₂（SA）（Ru-1）和Ru（dmp）₂（SA）（Ru-2）的两个新Ru（II）配合物（dip = 4,7-diphenyl合成-1,10-菲咯啉; dmp = 2,9-二甲基-1,10-菲咯啉; SA =水杨酸酯）以评估其体外细胞毒性。发现这些复合物对不同类型的人类癌症表现出中等的抗肿瘤活性，包括A549（人类肺癌），MCF-7（乳腺癌），HeLa（人类宫颈癌）和HepG2（人类肝细胞癌）细胞系，但与顺铂相比，对人正常细胞BEAS-2B（永生化的人支气管上皮细胞）的毒性低。进一步的研究表明，这些复合物可以诱导A549细胞凋亡，包括激活半胱天冬酶家族蛋白和聚（ADP-核糖）聚合酶（PARP），降低Bcl-2 / Bax和Bcl-xl / Bad比例，增强细胞活性氧（ ROS）的积累，触发DNA损伤，降低线粒体膜电位（MMP），并导致线粒体细胞色素c释放。值得注意的是，复杂Ru-1对发育中的斑马鱼胚胎显示出低毒性。所获得的结果表明，这些新的合成复合物具有被开发为肺癌治疗的低毒剂的潜力。