School of Pharmacy, Guangdong Medical University, Dongguan 523808, China; Pharmacy Department, The People's Hospital of Gaozhou, Maoming 525200, China.
School of Pharmacy, Guangdong Medical University, Dongguan 523808, China.
J Inorg Biochem. 2021 Jun;219:111450. doi: 10.1016/j.jinorgbio.2021.111450. Epub 2021 Mar 29.
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)L]PF; Ir2: [Ir(bzq)L]PF; Ir3: [Ir(dfppy)L]PF; Ir4: [Ir(thpy)L]PF; 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.
线粒体损伤会阻碍细胞的能量产生，并产生过多的 ROS（活性氧），通过自噬或细胞凋亡导致细胞死亡。在本文中，我们合成并表征了四个环金属化铱（III）配合物（Ir1：[Ir(piq)L]PF；Ir2：[Ir(bzq)L]PF；Ir3：[Ir(dfppy)L]PF；Ir4：[Ir(thpy)L]PF；piq = 1-苯基异喹啉；bzq = 苯并[h]喹啉；dfppy = 2-(2,4-二氟苯基)吡啶；thpy = 2-(2-噻吩基)吡啶；L = 1,10-菲咯啉-5-胺）。细胞毒性试验表明，这些配合物对癌细胞具有优异的细胞毒性，机制研究表明这些配合物可以特异性靶向线粒体。配合物 Ir1 和 Ir2 可以破坏线粒体的功能，随后增加细胞内 ROS 水平，降低 MMP（线粒体膜电位）并干扰 ATP 能量产生，导致自噬和细胞凋亡。此外，Ir1 和 Ir2 诱导的自噬与细胞凋亡协同促进细胞死亡。令人惊讶的是，这四个配合物对金黄色葡萄球菌和铜绿假单胞菌也表现出适度的抗菌活性。
