👤 Liu ZL

A new class of luminescent Ir^III antitumor agents, namely, [Ir(CP1)(PY1)₂] (Ir-1), [Ir(CP1)(PY2)₂] (Ir-2), [Ir(CP1)(PY4)₂] (Ir-3), [Ir(CP2)(PY1)₂] (Ir-4), [Ir(CP2)(PY4)₂] (Ir-5), [Ir(CP3)(PY1)₂]⋅CH₃OH (Ir-6), [Ir(CP4)(PY4)₂]⋅CH₃OH (Ir-7), [Ir(CP5)(PY2)₂] (Ir-8), [Ir(CP5)(PY4)₂]⋅CH₃OH (Ir-9), [Ir(CP6)(PY1)₂] (Ir-10), [Ir(CP6)(PY2)₂]⋅CH₃OH (Ir-11), [Ir(CP6)(PY3)₂] (Ir-12), [Ir(CP6)(PY41)₂] (Ir-13), and [Ir(CP7)(PY1)₂] (Ir-14), supported by 8-oxychinolin derivatives and 1-phenylpyrazole ligands was prepared. Compared with SK-OV-3/DDP and HL-7702 cells, the Ir-1-Ir-14 compounds exhibited half maximal inhibitory concentration (IC₅₀) values within the high nanomolar range (50 nM-10.99 μM) in HeLa cells. In addition, Ir-1 and Ir-3 accumulated and stained the mitochondrial inner membrane of HeLa cells with high selectivity and exhibited a high antineoplastic activity in the entire cervical HeLa cells, with IC₅₀ values of 1.22 ± 0.36 μM and 0.05 ± 0.04 μM, respectively. This phenomenon induced mitochondrial dysfunction, suggesting that these cyclometalated Ir^III complexes can be potentially used in biomedical imaging and Ir(III)-based anticancer drugs. Furthermore, the high cytotoxicity activity of Ir-3 is correlated with the 1-phenylpyrazole (H-PY4) secondary ligands in the luminescent Ir^III antitumor complex. Show less

This paper reports the synthesis, structure characterization, and anticancer properties of 13 organometallic Ru(ii)-arene complexes: [Ru(η6-p-cymene)Cl-(L1)] (1), [Ru(η6-p-cymene)Cl-(L2)] (2), [Ru(η6-p-cymene)Cl-(L3)] (3), [Ru(η6-p-cymene)Cl-(L4)] (4), [Ru(η6-p-cymene)Cl-(L5)] (5), [Ru(η6-p-cymene)I-(L1)] (6), [Ru(η6-p-cymene)I-(L2)] (7), [Ru(η6-p-cymene)I-(L3)] (8), [Ru(η6-p-cymene)I-(L4)] (9), [Ru(η6-p-cymene)I-(L5)] (10), [Ru(η6-p-cymene)I-(L6)] (11), [Ru(η6-p-cymene)I-(L7)] (12), and [Ru(η6-p-cymene)Cl-(L8)] (13) respectively containing deprotonated 5,7-dichloro-2-methyl-8-quinolinol (H-L1), 5,7-dibromo-2-methyl-8-quinolinol (H-L2), 5-chloro-7-iodo-8-hydroxy-quinoline (H-L3), 5,7-dibromo-8-quinolinol (H-L4), 5,7-diiodo-8-hydroxyquinoline (H-L5), 8-hydroxy-2-methylquinoline (H-L6), 2,8-quinolinediol (H-L7), or 6,7-dichloro-5,8-quinolinedione (H-L8). MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay showed that 13 organometallic Ru(ii)-arene complexes 1-13 are more selective for HeLa cells than normal HL-7702 cells. In addition, 1, 2, 5, and 6, which contain the active ligands H-L1 and H-L2, showed remarkable cell cytotoxicity, giving the respective IC50 values of 2.00 ± 0.20 nM, 0.89 ± 0.62 μM, 25.00 ± 0.30 nM, and 2.18 ± 0.35 μM on HeLa cancer cells. These values indicated higher activity than 6,7-dichloro-5,8-quinolinedione and other 8-hydroxyquinoline derivative Ru(ii)-arene complexes. Interestingly, all these Ru(ii)-arene complexes 1-13 were significantly less toxic to human hepatic (HL-7702) cells. Moreover, 1- and 2-induced HeLa cell apoptosis was mediated by the inhibition of telomerase activity and dysfunction of mitochondria, and resulted in DNA damage and increased anti-migration activity on HeLa cells. The organometallic Ru(ii)-arene complex 1 exhibited evident priority to the antitumor activity compared to 2, which should be highly associated with the key roles of the 5,7-dichloro substituted groups in the L1 ligand of organometallic Ru(ii)-arene complexes 1. Remarkably, 1 showed higher inhibitory activity against the xenograft tumor growth of human cervical cells (HeLa) in vivo (tumor growth inhibition rate (TGIR) = 58.5%) than cisplatin. This study was the first to show that the 5,7-dihalogenated-2-methyl-8-quinolinol organometallic Ru(ii)-arene complexes 1 and 2 are novel Ru(ii) anticancer drug candidates. Show less

A rhodium(iii) complex, [Rh(MQ)(DMSO)₂Cl₂] (1), with 8-hydroxy-2-methylquinoline as the ligand was synthesized and characterized. Complex 1 exhibited cytotoxicity against BEL-7404, Hep-G2, NCI-H460, T-24, and A549 cell lines with IC₅₀ values in the micromolar range (6.52-17.86 μM). Various experiments on the Hep-G2 cells showed that complex 1 caused cell cycle arrest at the S phase, downregulation of cdc25 A, cyclin A, cyclin B and CDK2, and upregulation of p21, p27 and p53. Furthermore, cytotoxicity mechanism studies suggested that complex 1-induced apoptosis was achieved via disruption of the mitochondrial function, which led to a significant loss of the mitochondrial membrane potential, an increase in the cellular levels of reactive oxygen species, cytochrome c, and apaf-1, and a fluctuation of the intracellular Ca²⁺ concentration. Taken altogether, complex 1 can trigger cancer cell death by inducing apoptosis through a mitochondrial dysfunction pathway. Show less