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

A series of arene Ru(II) complexes, [(η6-MeC6H5)Ru(L)Cl]Cl, (L=o-ClPIP,1;m-ClPIP,2andp-ClPIP,3) (o-ClPIP=2-(2-chlorophenyl)imidazo[4,5-f][1,10]phenanthroline;m-ClPIP=2-(3-chlorophenyl)imidazo[4,5-f][1,10]phenanthroline;p-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 that1exhibits moderated binding affinity toKRASG-quadruplex DNA by groove mode. Further, in vitro studies reveal that1displays inhibitory activity against MCF-7 growth with IC50= 3.7 ± 0.2 μM. Flow cytometric analysis, comet assay, and immunofluorescence confirm that1can 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 stabilizingKRASG-quadruplex conformation on oncogene promoter.Keywords:arene ruthenium complex;KRASG-quadruplex DNA;breast cancer;apoptosis;DNA damage