Anticancer evaluation of ferrocene-modified half-sandwich ruthenium(II) acylhydrazone complexes against A549 cell...

Owing to the intrinsic drawbacks of platinum chemotherapeutics, ruthenium(II) complexes exhibited superior performance in mechanism of action, tumor selectivity, and systemic toxicity, thus establishing themselves as a prominent research frontier in non‑platinum metallodrug development. In this paper, four half-sandwich ruthenium(II) acylhydrazone complexes were designed and prepared. The introduction of ferrocene unit endowed these complexes with favorable in vitro anti-proliferative activity toward A549 cells. Even against cisplatin-resistant A549/DDP cells, these complexes still retain potent activity, which is favorable for overcoming the drug-resistance of cisplatin-based drugs and exploring their alternatives. Additionally, these complexes could target and impair the integrity of lysosomes, leading to the decrease in mitochondrial membrane potential, then following a lysosomal-mitochondrial apoptotic anticancer channel. This research not only offers valuable insights into designing highly efficient non‑platinum metallic anticancer drugs but also proposes a strategy for developing apoptotic inducers through lysosomal damage.