Fluorescent iridium(iii) coumarin-salicylaldehyde Schiff base compounds as lysosome-targeted antitumor agents.

Six fluorescent half-sandwich iridium(III) coumarin-salicylaldehyde Schiff base (O^N) compounds ([(η5-Cp*)Ir(O^N)Cl]) were prepared and characterized. The introduction of coumarin unit increased the antitumor activity (IC50: 9.9±0.1 μM ~ 40.7±12.9 μM) of these compounds, the best of which was nearly two times that of clinical cisplatin. Laser confocal shows compounds possessed an energy-dependent cellular uptake mechanism, accumulated in lysosomes (Pearson co-localization coefficient: ~0.7), damaged the integrity of lysosomes, and induce apoptosis. Compounds can decrease the mitochondrial membrane potential, catalyze the oxidation of coenzyme (nicotinamide-adenine dinucleotid) and improve the levels of intracellular reactive oxygen species, follow an antitumor mechanism of oxidation. Additionally, these compounds could block the metastasis of tumor cells. Above all, these iridium(III) compounds are potential antitumor agents with dual functions: lysosomal damage and anti-metastasis.