Preparation of ferrocene‑iridium(III) acylhydrazone complexes and their anticancer application against A549 cell line

Two ferrocene‑iridium(III) acylhydrazone complexes (Fe-Ir1 and Fe-Ir2) were designed and synthesized, which showed excellent anti-proliferative activity against A549 human lung adenocarcinoma and A549/DDP (cisplatin-resistant) cell lines, especially for Fe-Ir1 (IC₅₀ = 10.2 ± 0.4 μM, twice that of cisplatin). Meanwhile, Fe-Ir1 showed low toxicity to BEAS-2B cells (normal dividing human bronchial epithelial cells), indicating its favorable selectivity. Fe-Ir1 entered A549 cells following an non-energy-dependent pathway, targeted lysosomes, induced changes in lysosomal membrane permeability, reduced glycolytic stress, arrested cell cycle, then promoted early-stage apoptosis and effectively inhibited cell migration. Western blotting also showed that the Fe-Ir1 could promote the expression of Bax protein and inhibited Bcl-2 and PARP protein in A549 cells. In vivo experiments demonstrated that Fe-Ir1 had significant capabilities in inhibiting tumor growth, cancer cell metastasis and spread. In conclusion, Fe-Ir1 holds promise as a potential alternative to platinum-based drugs and warrants further research, offering more hope and vitality to cancer patients.