Polypyridyl Ruthenium(II) complex-induced mitochondrial membrane potential dissipation activates DNA damage-mediated apoptosis to inhibit liver cancer
| Autor: | Xuanhao Zhao, Qiong Wu, Xiaoting Huang, Li Li, Yumei Li, Gengnan Yu, Wenjie Mei |
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| Rok vydání: | 2018 |
| Předmět: |
DNA damage
Pyridines Cell chemistry.chemical_element Antineoplastic Agents Apoptosis Mitochondrion Inhibitory postsynaptic potential 01 natural sciences Ruthenium 03 medical and health sciences Coordination Complexes Cell Line Tumor Drug Discovery medicine Animals Humans Zebrafish 030304 developmental biology Cell Proliferation Pharmacology Membrane potential Membrane Potential Mitochondrial 0303 health sciences 010405 organic chemistry Organic Chemistry Liver Neoplasms General Medicine Hep G2 Cells 0104 chemical sciences medicine.anatomical_structure chemistry Cancer cell Biophysics Heterografts DNA Damage |
| Zdroj: | European journal of medicinal chemistry. 164 |
| ISSN: | 1768-3254 |
| Popis: | In this study, four polypyridyl ruthenium(II) complexes, namely, [(L1)2RuL2]·2ClO4 (1: L1 = phen, L2 = o-TFPIP, 2: L1 = bpy, L2 = o-TFPIP, 3: L1 = phen, L2 = o-MOPIP, and 4: L1 = bpy, L2 = o-MOPIP), were synthesized with different phenanthroimidazole derivatives, and their inhibitory activities were tested against various cancer cells. Among the Ru(II) complexes, 1 excellently inhibited the proliferation and induced the apoptosis of HepG2 cell. Importantly, 1 was mainly distributed in the cell mitochondria and markedly induced the dissipation of mitochondrial membrane potential, possibly attributing to DNA damage induced by the Ru(II) complexes. Synthetic Ru(II) complexes can suppress the growth of tumor cells in zebrafish xenograft model with low toxicity at effective concentrations. These results inspired us to further develop polypyridyl ruthenium(II) complexes as potential potent inhibitors against liver cancer. |
| Databáze: | OpenAIRE |
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