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 (- and -) with different ancillary ligands and a PARP-1-inhibitory chelating ligand 2-(2,3-dibromo-4,5-dimethoxybenzylidene)hydrazine-1-carbothioamide () were designed and prepared. The target complexes were structurally characterized by NMR and ESI-MS techniques. Among them, the crystal and molecular structures of and were also determined by X-ray crystallography. These complexes retained the PARP-1 enzyme inhibitory effect of and showed potent antiproliferative activity on the tested cancer cell lines. The ruthenium(II) complexes were found to be more cytotoxic than the iridium(III) complexes . Further investigations revealed that the most active complex 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.