Half-sandwich iridium(III) (IrIII) anticancer complexes, as promising alternatives to platinum-based drugs, especially for solving resistance to platinum drugs, have demonstrated excellent Show more
Half-sandwich iridium(III) (IrIII) anticancer complexes, as promising alternatives to platinum-based drugs, especially for solving resistance to platinum drugs, have demonstrated excellent application prospect. The potency of these IrIII complexes as anticancer agents could be significantly enhanced through the strategic modification of their peripheral ligands. In this study, four structurally varied triphenylamine (TPA)-modified half-sandwich IrIII Schiff base complexes were designed and prepared. The incorporation of TPA unit has effectively endowed these complexes with suitable emission, which facilitates the evaluation of intracellular accumulation and cell morphology. These complexes demonstrated favorable in vitro anti-proliferative activity against A549 cell line (lung cancer cells, derived from alveolar basal epithelial cells), especially for pentamethylcyclopentadiene (Cp*)-based one (IrTS1 and IrTS3), and that is almost 2.5-fold more than cisplatin under the same conditions. Meanwhile, IrTS1 and IrTS3 possessed excellent activity against A549/DDP (cisplatin-resistant) cell line and the similar cytotoxicity to cisplatin against BEAS-2B cell line (derived from the bronchial epithelium of normal human lungs), then following a mitochondria apoptotic channel. Show less
Title: Design and anticancer behaviour of cationic/neutral half-sandwich iridium(III) imidazole-phenanthroline/phenanthrene complexes.
Abstract: Considerable attention has been devoted to the explora Show more
Title: Design and anticancer behaviour of cationic/neutral half-sandwich iridium(III) imidazole-phenanthroline/phenanthrene complexes.
Abstract: Considerable attention has been devoted to the exploration of organometallic iridium(III) (IrIII) complexes for their potential as metallic anticancer drugs. In this study, twelve half-sandwich IrIII imidazole-phenanthroline/phenanthrene complexes were prepared and characterized. Complexes exhibited promising in-vitro anti-proliferative activity, and some are obviously superior to cisplatin towards A549 cells. These complexes possessed suitable fluorescence, and a non-energy-dependent uptake pathway was identified, subsequently leading to their accumulation in the lysosome and the lysosomal damage. Additionally, complexes could inhibit the cell cycle (G1-phase) and catalyze intracellular NADH oxidation, thus substantiating the elevation of intracellular reactive oxygen species (ROS) level, which confirming the oxidative mechanism. Western blotting further confirmed that complexes could induce A549 cell apoptosis through the lysosomal-mitochondrial anticancer pathway, which was inconsistent with cisplatin. In summary, these complexes offer fresh concepts for the development of organometallic non‑platinum anticancer drugs. Show less
Half-sandwich iridium(III) complexes show potential value in the anticancer field. However, complexes with favorable luminescence performance are rare, which limits further investigation of the antica Show more
Half-sandwich iridium(III) complexes show potential value in the anticancer field. However, complexes with favorable luminescence performance are rare, which limits further investigation of the anticancer mechanism. In this paper, 10 triphenylamine-modified fluorescent half-sandwich iridium(III) pyridine complexes {[(η5-Cpx)Ir(L)Cl2]} (Ir1-Ir10) were prepared and showed potential antiproliferative activity, effectively inhibiting the migration of A549 cells. Ir6, showing the best activity among these complexes, exhibited excellent fluorescence performance (absolute fluorescence quantum yield of 15.17%) in solution. Laser confocal detection showed that Ir6 followed an energy-dependent cellular uptake mechanism, specifically accumulating in mitochondria (Pearson co-localization coefficient of 0.95). A Western blot assay further confirmed the existence of a mitochondrial apoptotic channel. Additionally, Ir6 could arrest the cell cycle at the G2/M phase, catalyze NADH oxidation, reduce the mitochondrial membrane potential, induce an increase in the level of intracellular reactive oxygen species, and exhibit a mechanism of oxidation. An in vivo antitumor assay confirmed that Ir6 can effectively inhibit tumor growth and is safer than cisplatin. Show less
Four triphenylamine/carbazole-modified half-sandwich ruthenium(ii) compounds [(η6-p-cymene)Ru(N/O^N)Cl]0/+ with Schiff base chelating ligands (N/O^N) are synthesized and characte Show more
Four triphenylamine/carbazole-modified half-sandwich ruthenium(ii) compounds [(η6-p-cymene)Ru(N/O^N)Cl]0/+ with Schiff base chelating ligands (N/O^N) are synthesized and characterized. The introduction of Schiff base units effectively increases the antitumor activity of these compounds (IC50: 1.70 ± 0.56-17.75 ± 3.10 μM), which, meanwhile, can inhibit the metastasis of tumor cells effectively. These compounds follow an energy-dependent cellular uptake mechanism, mainly accumulate in lysosomes to destroy their integrity, and then eventually promote apoptosis. In addition, these compounds can induce an increase of intracellular reactive oxygen species (ROS) levels and provide an antitumor mechanism of oxidation, which is confirmed by the decrease of mitochondrial membrane potential (MMP) and the catalytic oxidation of the coenzyme nicotinamide-adenine dinucleotide (NADH). All these indicate that these ruthenium(ii) compounds are expected to be dual-functional antitumor agents: anti-metastasis and lysosomal damage. Show less
A series of half-sandwich structural iridium(III) phenanthroline (Phen) complexes with halide ions (Cl- , Br- , I- ) and pyridine leaving groups ([(η5 -CpShow more
A series of half-sandwich structural iridium(III) phenanthroline (Phen) complexes with halide ions (Cl- , Br- , I- ) and pyridine leaving groups ([(η5 -CpX )Ir(Phen)Z](PF6 )n , Cpx : electron-rich cyclopentadienyl group, Z: leaving group) have been prepared. Target complexes, especially the Cpxbiph (biphenyl-substituted cyclopentadienyl)-based one, showed favourable anticancer activity against human lung cancer (A549) cells; the best one (Ir8) was almost five times that of cisplatin under the same conditions. Compared with complexes involving halide ion leaving groups, the pyridine-based one did not display hydrolysis but effectively caused lysosomal damage, leading to accumulation in the cytosol, inducing an increase in the level of intracellular reactive oxygen species and apoptosis; this indicated an anticancer mechanism of oxidation. Additionally, these complexes could bind to serum albumin through a static quenching mechanism. The data highlight the potential value of half-sandwich iridium(III) phenanthroline complexes as anticancer drugs. Show less
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 a coumarin unit increased the Show more
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 a 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. The results of laser confocal microscopy demonstrated that these compounds possessed an energy-dependent cellular uptake mechanism, accumulated in the lysosomes (Pearson co-localization coefficient: ∼0.7), damaged the integrity of the lysosomes, and induced apoptosis. The compounds could also decrease the mitochondrial membrane potential, catalyze the oxidation of the coenzyme (nicotinamide-adenine dinucleotide) and improve the levels of the intracellular reactive oxygen species, following an antitumor mechanism of oxidation. Additionally, these compounds could block the metastasis of tumor cells. Above all, these iridium(iii) compounds show potential as antitumor agents with dual functions: lysosomal damage and anti-metastasis. Show less
Iridium(III) complexes have attracted more and more attention in the past few years because of their potential antineoplastic activity. In this study, four IrIII complexes of the types [(η< Show more
Iridium(III) complexes have attracted more and more attention in the past few years because of their potential antineoplastic activity. In this study, four IrIII complexes of the types [(η5 -Cpx )Ir(N^N)Cl]PF6 (complexes 1 and 2) and [Ir(Phpy)2 (N^N)]PF6 (complexes 3 and 4) have been synthesized and characterized. They exhibit potential antineoplastic activity towards A549 cells, especially in the case of complex 1 [IC50 =(3.56±0.5) μm], which was nearly six times as effective as cisplatin [(21.31±1.7) μm]. Additionally, these complexes show some selectivity towards cancer cells over normal cells. They could be transported by serum albumin (binding constants were changed from 0.37×105 to 81.71×105 m-1 ). IrIII complexes 1 and 2 could catalyze the transformation of nicotinamide adenine dinucleotide reduced form (NADH) into NAD+ (turnover numbers 43.2, 11.9] and induce the accumulation of reactive oxygen species, thus confirming their antineoplastic mechanism of oxidation, whereas the cyclometalated complexes 3 and 4 were able to target the lysosome [Pearson co-localization coefficient (PCC)=0.73], cause lysosomal damage, and induce apoptosis. Understanding the mechanism of action would help further structure-activity optimization on these IrIII complexes as emerging cancer therapeutics. Show less