Microwave-assisted synthesis of ruthenium(ii) complexes containing levofloxacin-induced G2/M phase arrest by triggering DNA damage

Abstract

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.