期刊
JOURNAL OF BIOLOGICAL INORGANIC CHEMISTRY
卷 24, 期 2, 页码 151-169出版社
SPRINGER
DOI: 10.1007/s00775-018-1635-8
关键词
Iridium(III) complexes; Apoptosis; Cell cycle distribution; Antibacterial activity; Western blot
资金
- National Nature Science Foundation of China [21877018]
- Natural Science Foundation of Guangdong Province [2016A030313728]
Three iridium(III) polypyridyl complexes [Ir(ppy)(2)(PYTA)](PF6) (1) (ppy=2-phenylpyridine), [Ir(bzq)(2)(PYTA)](PF6) (2) (bzq=benzo[h]quinolone) and [Ir(piq)(2)(PYTA)](PF6) (3) (piq=1-phenylisoquinoline, PYTA=2,4-diamino-6-(2-pyridyl)-1,3,5-triazine) were synthesized and characterized by elemental analysis, IR, H-1 NMR and C-13 NMR. The cytotoxic activity of the complexes toward cancer SGC-7901, Eca-109, A549, HeLa, HepG2, BEL-7402 and normal LO2 cell lines was investigated by 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) method. Complex 3 shows the most effective on inhibiting the above cell growth among these complexes. The complexes locate at the lysosomes and mitochondria. AO/EB, Annex V and PI and comet assays indicate that the complexes can induce apoptosis in SGC-7901 cells. Intracellular ROS and mitochondrial membrane potential were examined under fluorescence microscopy. The results demonstrate that the complexes increase the intracellular ROS levels and induce a decrease in the mitochondrial membrane potential. The complexes can enhance intracellular Ca2+ concentration and cause a release of cytochrome c. The autophagy was studied using MDC staining and western blot. Complexes 1-3 can effectively inhibit the cell invasion with a concentration-dependent manner. Additionally, the complexes target tubules and inhibit the polymerization of tubules. The antimicrobial activity of the complexes against S. aureus, E. coli, Salmonella and L. monocytogenes was explored. The mechanism shows that the complexes induce apoptosis in SGC-7901 cells through ROS-mediated lysosomal-mitochondrial, targeting tubules and damage DNA pathways.Graphical AbstractThree iridium(III) complexes [Ir(N-C)(2)(PYTA)](PF6) (N-C=ppy, 1; bzq, 2; piq, 3) were synthesized and characterized. The anticancer activity of the complexes against SGC-7901 cells was studied by apoptosis, comet assay, autophagy, ROS, mitochondrial membrane potential, intracellular Ca2+ levels, release of cytochrome c, tubules and western blot analysis. The antibacterial activity in vitro was also assayed. [GRAPHICS] .
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