Cyclometalated iridium(III) complexes as mitochondria-targeted anticancer and antibacterial agents to induce both autophagy and apoptosis

• Published in: Journal of inorganic biochemistry 2021-06, Vol.219, p.111450-111450, Article 111450
• Main Authors: Chen, Bing-Bing, Pan, Nan-Lian, Liao, Jia-Xin, Huang, Min-Ying, Jiang, Dong-Chun, Wang, Jun-Jie, Qiu, Hai-Jun, Chen, Jia-Xi, Li, Lin, Sun, Jing
• Format: Article
• Language: English
• Subjects: A549 Cells; Anti-Bacterial Agents - chemistry; Anti-Bacterial Agents - pharmacology; Antibacterial; Anticancer; Antineoplastic Agents - chemistry; Antineoplastic Agents - pharmacology; Apoptosis; Apoptosis - drug effects; Autophagy; Autophagy - drug effects; Cell Line, Tumor; Cell Movement - drug effects; Coordination Complexes - chemistry; Coordination Complexes - pharmacology; Humans; Iridium - chemistry; Iridium(III) complexes; Magnetic Resonance Spectroscopy - methods; Membrane Potential, Mitochondrial - drug effects; Mitochondria; Mitochondria - metabolism; Pseudomonas aeruginosa - drug effects; Quinolines - chemistry; Reactive Oxygen Species - metabolism; Spectrometry, Mass, Electrospray Ionization - methods; Staphylococcus aureus - drug effects
• ISSN: 0162-0134; 1873-3344
• DOI: 10.1016/j.jinorgbio.2021.111450

Mitochondrial damage will hinder the energy production of cells and produce excessive ROS (reactive oxygen species), resulting in cell death through autophagy or apoptosis. In this paper, four cyclometalated iridium(III) complexes (Ir1: [Ir(piq)2L]PF6; Ir2: [Ir(bzq)2L]PF6; Ir3: [Ir(dfppy)2L]PF6; Ir4: [Ir(thpy)2L]PF6; piq = 1-phenylisoquinoline; bzq = benzo[h]quinoline; dfppy = 2-(2,4-difluorophenyl)pyridine;thpy = 2-(2-thienyl)pyridine; L = 1,10-phenanthroline-5-amine) were synthesized and characterized. Cytotoxicity tests show that these complexes have excellent cytotoxicity to cancer cells, and mechanism studies indicatethat these complexes can specifically target mitochondria. Complexes Ir1 and Ir2 can damage the function of mitochondria, subsequently increasing intracellular levels of ROS, decreasing MMP (mitochondrial membrane potential), and interfering with ATP energy production, which leads to autophagy and apoptosis. Furthermore, autophagy induced by Ir1 and Ir2 can promote cell death in coordination with apoptosis. Surprisingly, these four complexes also showed moderate antibacterial activity to S. aureusand P. aeruginosa. Mitochondria-targeted cyclometalated iridium(III) complexes induced autophagy and apoptosis at the same time, and showed antibacterial activity to S. Aureus and P. Aeruginosa. [Display omitted] •Four Ir(III) complexes having 1,10-phenanthroline-5-amine (L) as a ligand were synthesized.•Ir1 is [Ir(1-phenylisoquinoline)2L]PF6 and Ir2 is [Ir(benzo[h]quinolone)2L]PF6.•All complexes demonstrate anticancer activity against tested human cancer cell lines.•Ir1 and Ir2, mainly located in mitochondria, could induce autophagy and apoptosis.•All complexes exhibited antibacterial activity against S. Aureus and P. Aeruginosa.