X-ray fluorescence imaging of single human cancer cells reveals that the N-heterocyclic ligands of iodinated analogues of ruthenium anticancer drugs remain coordinated after cellular uptake.
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.
School of Chemistry and Physics, The University of Adelaide, Adelaide, SA, 5005, Australia.
Sumy
S
Antony
Jade B
JB
Aitken
Stefan
S
Vogt
Barry
B
Lai
Tracey
T
Brown
Leone
L
Spiccia
Hugh H
HH
Harris
D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000378:metabolism / Q000493:pharmacokinetics; D001692:Biological Transport; D002448:Cell Adhesion; D045744:Cell Line, Tumor; D006571:Heterocyclic Compounds / Q000737:chemistry*; D006801:Humans; D007455:Iodine / Q000737:chemistry*; D008024:Ligands; D009369:Neoplasms / Q000378:metabolism* / Q000473:pathology; D061848:Optical Imaging; D009942:Organometallic Compounds / Q000138:chemical synthesis / Q000737:chemistry* / Q000378:metabolism* / Q000493:pharmacokinetics; D000644:Quaternary Ammonium Compounds / Q000737:chemistry; D012428:Ruthenium / Q000737:chemistry*; D059010:Single-Cell Analysis; D014965:X-Rays
D000970:Antineoplastic Agents; D006571:Heterocyclic Compounds; D008024:Ligands; D009942:Organometallic Compounds; D000644:Quaternary Ammonium Compounds; D012428:Ruthenium; D007455:Iodine; C027917:tetramethylammonium