Journal
JOURNAL OF INORGANIC BIOCHEMISTRY
Volume 249, Issue -, Pages -Publisher
ELSEVIER SCIENCE INC
DOI: 10.1016/j.jinorgbio.2023.112393
Keywords
Ferrocene; Anticancer; Non-platinum drugs; Lysosome-targeted; Apoptosis; IrIII complex
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Half-sandwich IrIII-Fc heteronuclear metal complexes exhibit promising anticancer activity and possess a different mechanism from platinum-based drugs, indicating their potential as alternative agents.
Half-sandwich iridium(III) (IrIII) complexes and ferrocenyl (Fc) derivatives are becoming the research hotspot in the field of anticancer because of their good bioactivity and unique anticancer mechanism different from platinum-based drugs. Then, a series of half-sandwich IrIII-Fc pyridine complexes have been prepared through the structural regulation in this study. The incorporation of half-sandwich IrIII complex with Fc unit successfully improves their anticancer activity, and the optimal performance (IrFc5) is almost 3-fold higher than that of cisplatin against A549 cells, meanwhile, which also shows better anti-proliferative activity against A549/DDP cells. Complexes can aggregate in the intracellular lysosome of A549 cells and induce lysosomal damage, disrupt the cell cycle, increase the level of intracellular reactive oxygen species, and eventually lead to cell apoptosis. Half-sandwich IrIII-Fc heteronuclear metal complexes possess a different anticancer mechanism from cisplatin, which can serve as a potential alternative to platinum-based drugs and show a good application prospect.
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