No abstract

The reasonable design of binuclear or multinuclear metal complexes has demonstrated their potential advantages in the field of anticancer. Herein, three heterobimetallic Ir(III)-Re(I) complexes, [Ir(C^N)2LRe(CO)3DIP](PF6)2 (C^N = 2-phenylpyridine (ppy, in...

The development of heteronuclear metal complexes as potent anticancer agents has received increasing attention in recent years. In this study, two new heteronuclear Ru(Ⅱ)-Re(Ⅰ) metal complexes, [Ru(bpy)2LRe(CO)3(DIP)](PF6)3 and [Ru(phen)2LRe(CO)3(DIP)](PF6)3 [RuRe-1 and RuRe-2, L = 2-(4-pyridinyl)imidazolio[4,5-f][1,10]phenanthroline, bpy = 2,2′-bipyridine, DIP = 4,7-diphenyl-1,10-phenanthroline, phen = 1,10-phenanthroline], were synthesized and characterized. Cytotoxicity assay shows that RuRe-1 and RuRe-2 exhibit higher anticancer activity than cisplatin, and exist certain selectivity toward human cancer cells over normal cells. The anticancer mechanistic studies reveal that RuRe-1 and RuRe-2 can induce apoptosis through the regulation of cell cycle, depolarization of mitochondrial membrane potential (MMP), elevation of intracellular reactive oxygen species (ROS), and caspase cascade. Moreover, RuRe-1 and RuRe-2 can effectively inhibit cell migration and colony formation. Taken together, heteronuclear Ru(Ⅱ)-Re(Ⅰ) metal complexes possess the prospect of developing new anticancer agents with high efficacy.

As an ideal scaffold for metal ion chelation, 8-hydroxyquinoline (8HQ) can chelate different metal ions, such as Fe2+, Cu2+, Zn2+, etc. Here, by integrating 8HQ with ruthenium(II) polypyridyl moiety, two...

A series of cyclometalated iridium(III) complexes with the formula [Ir(C^N)2 L](PF6) (C^N = 2-phenylpyridine (ppy, in Ir-1), 2-(2-thienyl)pyridine (thpy, in Ir-2), 2-(2,4-difluorophenyl)pyridine (dfppy, in Ir-3), L = 2-(1H-imidazo[4,5-f][1,10]phenanthrolin-2-yl)quinolin-8-ol) were designed and synthesized, which utilize 8-hydroxyquinoline derivative as N^N ligands to chelate the cofactor Fe2+ of the Jumonji domain-containing protein (JMJD) histone demethylase. As expected, the results of UV/Vis titration analysis confirm the chelating capabilities of Ir-1–3 for Fe2+, and molecular docking studies also show that Ir-1–3 can interact with the active pocket of JMJD protein, and treatment of cells with Ir-1–3 results in significant upregulation of trimethylated histone 3 lysine 9 (H3K9Me3), indicating the inhibition of JMJD activity. Meanwhile, Ir-1–3 exhibit much higher cytotoxicity against the tested tumor cell lines compared with the clinical chemotherapeutic agent cisplatin. And Ir-1–3 can block the cell cycle at G2/M phase and inhibit cell migration and colony formation. Further studies show that Ir-1–3 can specifically accumulate in lysosomes, damage the integrity of lysosomes, and induce apoptosis and autophagy. Reduction of mitochondrial membrane potential (MMP) and elevation of reactive oxygen species (ROS) also contribute to the antitumor effects of Ir-1–3. Finally, Ir-1 can inhibit tumor growth effectively in vivo and increase the expression of H3K9Me3 in tumor tissues. Our study demonstrates that these iridium(III) complexes are promising anticancer agents with multiple functions, including the inhibition of JMJD and induction of apoptosis and autophagy.