Ru(II) complexes have attracted increasing attention as promising antitumor agents for their relatively low toxicity, high affinity to DNA molecules, and correlation with multiple targets. Meanwhile, quinolones are synthetic antibacterial agents widely used in the clinical practice. In this paper, two novel Ru(II) complexes coordinated by levofloxacin (LOFLX), [Ru(bpy)₂(LOFLX)]·2ClO₄ (1), and [Ru(dmbpy)₂(LOFLX)]·2ClO₄ (2) (bpy = 2,2′-bipyridine, dmbpy = 4,4′-dimethyl-2,2′-bipyridine) were synthesized with high efficiency under microwave irradiation and characterized by ESI-MS, ¹H NMR, and ¹³C NMR. The binding behavior of these complexes with double-strand calf thymus DNA(CT-DNA) was investigated using spectroscopy, molecular docking, and density functional theory calculations. Results showed that 2 exhibited higher binding affinity than 1 and LOFLX. Further studies showed that 2 could induce the G2/M phase arrest of A549 cells via DNA damage. In summary, these results indicated that 2 could be developed as a potential anticancer agent in treatment of lung cancer through the induction of cell cycle arrest at G2/M phase by triggering DNA damage.

中文翻译：

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微波辅助合成含有左氧氟沙星的钌 (II) 配合物通过触发 DNA 损伤诱导 G2/M 期阻滞

Ru( II )配合物因其毒性相对较低、对DNA分子的亲和力高以及与多个靶点的相关性而作为有前途的抗肿瘤剂而受到越来越多的关注。同时，喹诺酮类药物是临床上广泛使用的合成抗菌剂。本文研究了左氧氟沙星（ LOFLX ）配位的两种新型Ru( II )配合物[Ru(bpy) ₂ (LOFLX)]·2ClO ₄ ( 1 )和[Ru(dmbpy) ₂ (LOFLX)]·2ClO ₄ ( 2 ) (bpy = 2,2'-bipyridine, dmbpy = 4,4'-dimethyl-2,2'-bipyridine) 在微波辐射下高效合成并通过 ESI-MS 进行表征, ¹H NMR和¹³ C NMR。使用光谱学、分子对接和密度泛函理论计算研究了这些复合物与双链小牛胸腺DNA(CT-DNA)的结合行为。结果表明，2表现出比1和LOFLX 更高的结合亲和力。进一步的研究表明，2可以通过DNA 损伤诱导 A549 细胞的 G2/M 期停滞。总之，这些结果表明，通过触发 DNA 损伤，诱导 G2/M 期细胞周期停滞， 2可被开发为治疗肺癌的潜在抗癌剂。