Arene Ru(II) Complexes Acted as Potential G-Quadruplex DNA Stabilizer Induced DNA Damage Mediated Apoptosis to Inhibit Breast Cancer Progress.

A series of arene Ru(II) complexes, [(-MeCH)Ru(L)Cl]Cl, (L=-ClPIP, ; -ClPIP, and -ClPIP, ) (-ClPIP=2-(2-chlorophenyl)imidazo[4,5-f][1,10]phenanthroline; -ClPIP=2-(3-chlorophenyl)imidazo[4,5-f][1,10]phenanthroline; -ClPIP=2-(4-chlorophenyl)imidazo[4,5-f][1,10]phenanthroline) was synthesized and investigated as a potential apoptosis inducer in chemotherapy. Spectroscopy and molecular docking simulations show that exhibits moderated binding affinity to G-quadruplex DNA by groove mode. Further, in vitro studies reveal that displays inhibitory activity against MCF-7 growth with IC = 3.7 ± 0.2 μM. Flow cytometric analysis, comet assay, and immunofluorescence confirm that can induce the apoptosis of MCF-7 cells and G0/G1 phase arrest through DNA damage. In summary, the prepared arene Ru(II) complexes can be developed as a promising candidate for targeting G-quadruplex structure to induce the apoptosis of breast cancer cells via binding and stabilizing G-quadruplex conformation on oncogene promoter.