Ferrocene-modified half-sandwich iridium(III) and ruthenium(II) propionylhydrazone complexes and anticancer application.

Ferrocene, ruthenium(II) and iridium(III) organometallic complexes, potential substitutes for platinum-based drugs, have shown good application prospects in the field of cancer therapy. Therefore, in this paper, six ferrocene-modified half-sandwich ruthenium(II) and iridium(III) propionylhydrazone complexes were prepared, and the anticancer potential was evaluated and compared with cisplatin. These complexes showed potential in-vitro anti-proliferative activity against A549 cancer cells, especially for Ir-based complexes, and showing favorable synergistic anticancer effect. Meanwhile, these complexes showed little cytotoxicity and effective anti-migration activity. Ir3, the most active complex (ferrocene-appended iridium(III) complex), could accumulate in the intracellular mitochondria, disturb the cell cycle (S-phase), induce the accumulation of reactive oxygen species, and eventually cause the apoptosis of A549 cells. Then, the design of these complexes provides a good structural basis for the multi-active non­platinum organometallic anticancer complexes.

The anticancer application of half-sandwich iridium(III) ferrocene-thiosemicarbazide Schiff base complexes.

Ferrocenyl derivatives and organometallic iridium(III) complexes have been prospective substitutes for platinum-based anticancer drugs. Eight half-sandwich iridium(III) ferrocene-thiosemicarbazide (Fc-TSC) Schiff base anticancer complexes were prepared in this study. These complexes displayed a dimeric structure and exhibited a particular fluorescence due to the "enol" orientation of the TSC pro-ligand. An energy-dependent pathway of the uptake mechanism was ascertained, which ended in the lysosome and led to lysosome damage and apoptosis. Flow cytometry confirmed that the complexes could block the cell cycle (G1 phase) and improve the levels of intracellular reactive oxygen species, indicating an anticancer mechanism of oxidation. Then, a lysosomal-mitochondrial anticancer pathway was verified through western blotting. In vivo toxicity assays confirmed that these complexes showed better anti-migration ability and less toxicity in comparison to cisplatin. Thus, these complexes provide a new strategy for the design of non-platinum organometallic anticancer drugs.

Configurationally regulated half-sandwich iridium(III)-ferrocene heteronuclear metal complexes: Potential anticancer 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.

Anticancer application of ferrocene appended configuration-regulated half-sandwich iridium(III) pyridine complexes.

Ferrocenyl derivatives and half-sandwich iridium(III) complexes have received extensive attention in the field of anticancer. In this paper, series of configuration-controlled ferrocene-modified half-sandwich iridium(III) pyridine complexes were prepared. The combination of half-sandwich iridium(III) complexes and ferrocenyl unit successfully improved the anticancer activity of these complexes, especially for trans-configurational one towards A549 cells, and the best-performing (FeIr5) was almost 3.5 times more potent than that of cisplatin. In addition, these complexes could inhibit the migration of A549 cells. Complexes can accumulate in intracellular lysosomes (PCC: >0.75), induce lysosomal damage, disturb the cell circle, decrease the mitochondrial membrane potential, improve the intracellular reactive oxygen species (ROS) levels, and eventually lead to apoptosis. Meanwhile, complexes could bind to serum protein following a static quenching mechanism and transport through it. Then, ferrocene-modified half-sandwich iridium(III) pyridine complexes hold the promise as potential organometallic anticancer agents for further investigation.