Mitochondria-targeted phosphorescent cyclometalated iridium(III) complexes: synthesis, characterization, and anticancer properties

• Published in: Journal of biological inorganic chemistry Vol. 25; no. 4; pp. 597 - 607
• Main Authors: Li, Yi, Liu, Ben, Xu, Cui-Xia, He, Liang, Wan, Yi-Chao, Ji, Liang-Nian, Mao, Zong-Wan
• Format: Journal Article
• Language: English
• Published: Berlin/Heidelberg Springer Berlin Heidelberg 01.06.2020; Springer Nature B.V
• Subjects: Antineoplastic Agents - chemical synthesis; Antineoplastic Agents - chemistry; Antineoplastic Agents - pharmacology; Antitumor agents; Apoptosis; Apoptosis - drug effects; Biochemistry; Biomedical and Life Sciences; Cancer; Caspase; Cell Line; Cell Proliferation - drug effects; Cisplatin; Coordination Complexes - chemical synthesis; Coordination Complexes - chemistry; Coordination Complexes - pharmacology; Depolarization; Dose-Response Relationship, Drug; Drug Screening Assays, Antitumor; Humans; Intracellular; Iridium - chemistry; Iridium - pharmacology; Life Sciences; Membrane potential; Microbiology; Mitochondria; Mitochondria - drug effects; Mitochondria - metabolism; Molecular Structure; Original Paper; Reactive oxygen species; Reactive Oxygen Species - analysis; Reactive Oxygen Species - metabolism; Structure-Activity Relationship; Iridium complex; Mitochondria targeted; Anticancer; Phosphorescent
• ISSN: 0949-8257; 1432-1327
• DOI: 10.1007/s00775-020-01783-2

Cyclometalated iridium(III) complexes represent a promising approach to developing new anticancer metallodrugs. In this work, three phosphorescent cyclometalated iridium(III) complexes Ir1–Ir3 have been explored as mitochondria-targeted anticancer agents. All three complexes display higher antiproliferative activity than cisplatin against the cancer cells screened, and with the IC 50 values ranging from 0.23 to 5.6 μM. Colocalization studies showed that these complexes are mainly localized in the mitochondria. Mechanism studies show that these complexes exert their anticancer efficacy through initiating a series of events related to mitochondrial dysfunction, including depolarization of mitochondrial membrane potential (MMP), elevation of intracellular reactive oxygen species (ROS) levels, and induction of apoptosis. Graphic abstract Mitochondria-targted cyclometalated iridium complexes induce apoptosis through depolarized mitochondria, elevation of intracellular ROS and activated caspase.