Studies on the reactivity of organometallic Ru–, Rh– and Os–pta complexes with DNA model compounds

Dorcier, Antoine; Hartinger, Christian G.; Scopelliti, Rosario; Fish, Richard H.; Keppler, Bernhard K.; Dyson, Paul J.

doi:10.1016/j.jinorgbio.2007.10.016

Cited by 105 publications

(79 citation statements)

References 43 publications

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“…The reaction of 5'-GMP can easily be monitored in 1 H NMR spectroscopy due to the shift of the N7 atom of 5'-GMP from d = 8.1 to approximately 7.9 ppm. [41] The reaction was completed within seconds and the adducts formed were stable in solution for more than 18 h. Accordingly, DNA is a possible target for these Ru ii -cymene complexes, as suggested for related organometallic ruthenium(II) compounds. [19] However, many drugs are administered intravenously, and amino acids and proteins are the first potential binding partners for the complexes in the bloodstream.…”

Section: Resultsmentioning

confidence: 94%

Maltol‐Derived Ruthenium–Cymene Complexes with Tumor Inhibiting Properties: The Impact of Ligand–Metal Bond Stability on Anticancer Activity In Vitro

Kandioller

Hartinger

Nazarov

et al. 2009

Chemistry A European J

119

104

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Organometallic ruthenium-arene compounds bearing a maltol ligand have been shown to be nearly inactive in in vitro anticancer assays, presumably due to the formation of dimeric Ru(II) species in aqueous solutions. In an attempt to stabilize such complexes, [Ru(eta(6)-p-cymene)(XY)Cl] (XY=pyrones or thiopyrones) complexes with different substitution pattern of the (thio)pyrone ligands have been synthesized, their structures characterized spectroscopically, and their aquation behavior investigated as well as their tumor-inhibiting potency. The aquation behavior of pyrone systems with electron-donating substituents and of thiopyrone complexes was found to be significantly different from that of the maltol-type complex reported previously. However, the formation of the dimer can be excluded as the primary reason for the inactivity of the complex because some of the stable compounds are not active in cancer cell lines either. In contrast, studies of their reactivity towards amino acids demonstrate different reactivities of the pyrone and thiopyrone complexes, and the higher stability of the latter probably renders them active against human tumor cells.

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Section: Resultsmentioning

confidence: 94%

Maltol‐Derived Ruthenium–Cymene Complexes with Tumor Inhibiting Properties: The Impact of Ligand–Metal Bond Stability on Anticancer Activity In Vitro

Kandioller

Hartinger

Nazarov

et al. 2009

Chemistry A European J

119

104

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“…In general, the potency of the RAPTA-Os analogues in vitro towards cancer cell lines is low, but they appear to be active toward solid metastatic tumours in vivo. 116,124,125 Recently, RAPTA-C, its osmium analogue as well as CpRh III Figure 18) also bearing three monodentate ligands are not active towards ovarian cancer cell lines up to a concentration of 100 µM. 127 They undergo rapid facile hydrolysis in two steps at 310 K, with the first aquation reaction (t 1/2 = ca.…”

Section: Figure 17mentioning

confidence: 99%

Designing organometallic compounds for catalysis and therapy

et al. 2012

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“…Note that neither ESIMS nor NMR spectroscopy provided evidence for a derivative in which two molecules of 9EtG are coordinated to the ruthenium center, which may be prevented by steric hindrance. [60] Cytotoxicity: The cytotoxicity of 1 and 4-6 (2 and 3 are not sufficiently soluble for in vitro testing) was studied in human SW480 colon adenocarcinoma, CH1, A2780 and cisplatin-resistant A2780 ovarian carcinoma, A549 lung carcinoma, Me300 melanoma, LNZ308 glioblastoma, and HCEC endothelial cell lines by means of the MTT cell survival assay. Concentration-effect curves for CH1 and SW480 cells are depicted in Figure 9, and their IC 50 values were determined after 96 h. Cytotoxicity of compounds 1, 4, and 5 towards the other cell lines are presented in Table 2 as IC 50 values determined after 72 h of incubation.…”

Section: Wwwchemeurjorgmentioning

confidence: 99%

In Vitro Anticancer Activity and Biologically Relevant Metabolization of Organometallic Ruthenium Complexes with Carbohydrate‐Based Ligands

Berger

Hanif

Nazarov

et al. 2008

Chemistry A European J

117

100

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The synthesis and in vitro anticancer activity of dihalogenido(eta6-p-cymene)(3,5,6-bicyclophosphite-alpha-D-glucofuranoside)ruthenium(II) complexes are described. The compounds were characterized by NMR spectroscopy and ESI mass spectrometry, and the molecular structures of dichlorido-, dibromido- and diiodido(eta6-p-cymene)(3,5,6-bicyclophosphite-1,2-O-isopropylidene-alpha-D-glucofuranoside)ruthenium(II) were determined by X-ray diffraction analysis. The complexes were shown to undergo aquation of the first halido ligand in aqueous solution, followed by hydrolysis of a P--O bond of the phosphite ligand, and finally formation of dinuclear species. The hydrolysis mechanism was confirmed by DFT calculations. The aquation of the complexes was markedly suppressed in 100 mM NaCl solution, and notably only very slow hydrolysis of the P--O bond was observed. The complexes showed affinity towards albumin and transferrin and monoadduct formation with 9-ethylguanine. In vitro studies revealed that the 3,5,6-bicyclophosphite-1,2-O-cyclohexylidene-alpha-D-glucofuranoside complex is the most cytotoxic compound in human cancer cell lines (IC50 values from 30 to 300 microM depending on the cell line).

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Studies on the reactivity of organometallic Ru–, Rh– and Os–pta complexes with DNA model compounds

Cited by 105 publications

References 43 publications

Maltol‐Derived Ruthenium–Cymene Complexes with Tumor Inhibiting Properties: The Impact of Ligand–Metal Bond Stability on Anticancer Activity In Vitro

Maltol‐Derived Ruthenium–Cymene Complexes with Tumor Inhibiting Properties: The Impact of Ligand–Metal Bond Stability on Anticancer Activity In Vitro

Designing organometallic compounds for catalysis and therapy

In Vitro Anticancer Activity and Biologically Relevant Metabolization of Organometallic Ruthenium Complexes with Carbohydrate‐Based Ligands

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