Design, Synthesis, and Anticancer Effect Studies of Iridium(III) Polypyridyl Complexes against SGC-7901 Cells

• Published in: Molecules (Basel, Switzerland) Switzerland), 2019-08, Vol.24 (17), p.3129
• Main Authors: Zhang, Li-Xia, Gu, Yi-Ying, Wang, Yang-Jie, Bai, Lan, Du, Fan, Zhang, Wen-Yao, He, Miao, Liu, Yun-Jun, Chen, Yan-Zhong
• Format: Article
• Language: English
• Subjects: A549 Cells; Acetonitrile; Animals; antitumor activity; Apoptosis; Bone marrow; Breast; Cancer therapies; Capillary tubes; Cell cycle; Cell death; Cell Line, Tumor; Cell Proliferation - drug effects; Cell Survival - drug effects; Cisplatin; Colon; Colon cancer; Coordination Complexes - chemical synthesis; Coordination Complexes - chemistry; Coordination Complexes - pharmacology; Cytotoxicity; Depolarization; DNA damage; Drug Design; Drug resistance; Drug Screening Assays, Antitumor; Electric potential; HeLa Cells; Hep G2 Cells; Humans; Inhibitory Concentration 50; Ionization; Iridium - chemistry; iridium(III) complexes; Liver cancer; Mass spectra; Membrane potential; Mice; Mitochondria; mitochondrial dysfunction; Nausea; NIH 3T3 Cells; NMR; Nuclear magnetic resonance; Pyridines - chemistry; Reactive Oxygen Species - metabolism; Room temperature; S phase; Spectrum analysis; Stomach Neoplasms - drug therapy; Stomach Neoplasms - metabolism; Voltage
• ISSN: 1420-3049; 1420-3049
• DOI: 10.3390/molecules24173129

Three iridium(III) complexes ([Ir(Hppy) (L)](PF ) (Hppy = 2-phenylpyridine, L = 5-nitrophenanthroline, NP), ; 5-nitro-6-amino-phenanthroline (NAP), ; and 5,6-diamino-phenanthroline (DAP) were synthesized and characterized. The cytotoxicities of Ir(III) complexes - against cancer cell lines SGC-7901, A549, HeLa, Eca-109, HepG2, BEL-7402, and normal NIH 3T3 cells were investigated using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-tetrazoliumbromide (MTT) method. The results showed that the three iridium(III) complexes had moderate in vitro anti-tumor activity toward SGC-7901 cells with IC values of 3.6 ± 0.1 µM for , 14.1 ± 0.5 µM for , and 11.1 ± 1.3 µM for . Further studies showed that - induce cell apoptosis/death through DNA damage, cell cycle arrest at the S or G0/G1 phase, ROS elevation, increased levels of Ca , high mitochondrial membrane depolarization, and cellular ATP depletion. Transwell and Colony-Forming assays revealed that complexes - can also effectively inhibit the metastasis and proliferation of tumor cells. These results demonstrate that - induce apoptosis in SGC-7901 cells through ROS-mediated mitochondrial damage and DNA damage pathways, as well as by inhibiting cell invasion, thereby exerting anti-tumor cell proliferation activity in vitro.