期刊
JOURNAL OF BIOLOGICAL INORGANIC CHEMISTRY
卷 18, 期 7, 页码 845-853出版社
SPRINGER
DOI: 10.1007/s00775-013-1027-z
关键词
Anticancer drugs; Ruthenium; Iodine; X-ray fluorescence imaging
资金
- Australian Research Council [DP0985807-QEII, DP0984722]
- International Synchrotron Access Program
- Australian Government
- US Department of Energy, Office of Science [DE-AC02-06CH11357]
- Australian Research Council [DP0984722] Funding Source: Australian Research Council
Analogues of KP1019 containing iodinated indazole ligands were prepared to investigate the biological fate of the Ru-N-heterocycle bond in this class of anticancer agents. The new complexes, 5-iodoindazolium trans-tetrachloridobis(5-iodoindazole)ruthen(III)ate (1) and 5-iodoindazolium trans-tetrachlorido(dimethyl sulfoxide)(5-iodoindazole)ruthen(III)ate (3), were characterized by elemental analysis, mass spectrometry and UV-vis spectrophotometry. Tetramethylammonium salts of these complexes (2 and 4) were synthesized and characterized in a similar manner. Half-maximum inhibitory concentrations of 2 and 4 with regard to A549 cells at 24 h were determined on the basis of the dose-response curves derived from real-time cell adhesion impedance measurements and were shown to be in the same range as those determined for KP1019 and NAMI-A using the same method. X-ray fluorescence imaging of single cultured A549 cells treated with 2 or 4 showed that, in both cases, the distribution of ruthenium and iodine was identical, indicating that the Ru-N bonds in the anionic complexes remained intact after incubation in culture medium and subsequent cellular uptake and processing.
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