Study on the Multimodal Anticancer Mechanism of Ru(II)/Ir(III) Complexes Bearing a Poly(ADP-ribose) Polymerase 1 Inhibitor

A series of novel ruthenium(II) and iridium(III) complexes (Ru1–Ru3 and Ir1–Ir3) with different ancillary ligands and a PARP-1-inhibitory chelating ligand 2-(2,3-dibromo-4,5-dimethoxybenzylidene)hydrazine-1-carbothioamide (L1) were designed and prepared. The target complexes were structurally characterized by NMR and ESI–MS techniques. Among them, the crystal and molecular structures of Ir1 and Ir2 were also determined by X-ray crystallography. These complexes retained the PARP-1 enzyme inhibitory effect of L1 and showed potent antiproliferative activity on the tested cancer cell lines. The ruthenium(II) complexes Ru1–Ru3 were found to be more cytotoxic than the iridium(III) complexes Ir1–Ir3. Further investigations revealed that the most active complex Ru3 induced apoptosis in MCF-7 cells by multiple modes, inclusive of inducing DNA damage, suppressing DNA damage repair, disturbing cell cycle distribution, decreasing the mitochondrial membrane potential, and increasing the intracellular reactive oxygen species levels.