Anticancer behaviour of simplified lysosome-targeted half-sandwich iridium(III) xanthate complexes towards A549 cell lines.

Although widely used clinically, the extensive nephrotoxicity and drug resistance of platinum-based metallic anticancer drugs have spurred the research and development of non‑platinum-based metallic anticancer drugs. Half-sandwich iridium(III) (IrIII) complexes have become a research hotspot in this field due to their excellent anticancer activity, structural tunability, and unique mechanism of action different from that of cisplatin. Then two half-sandwich IrIII xanthate complexes with a simple structure were prepared in this study. In vitro anti-proliferative evaluation showed that these two complexes enjoyed favorable activity towards A549 lung cancer cells in comparison to cisplatin, and could also effectively inhibit cell migration. Further research showed that Ir1 could target lysosomes (PCC: 0.85) and lead to lysosomal damage, then disturbing the cell cycle arrest (G0/G1 phase), decreasing mitochondrial membrane potential and inducing the improvement of intracellular reactive oxygen species levels. Western blotting also confirmed the existence of a lysosomal-mitochondrial apoptotic anticancer pathway. Collectively, these structurally simple yet highly active IrIII complexes provide a valuable foundation for the rational design and development of novel non‑platinum-based metallic anticancer drugs.