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            Ru Perspectives of Ruthenium Complexes in Cancer Therapy

Lentzen, Olivier; Moucheron, Cécile; Mesmaeker, Andrée Kirsch‐De

doi:10.1002/0470864052.ch19

Cited by 9 publications

(4 citation statements)

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“…2e, 3c, 3d, 4a, 4b, 5b, 5c Whether a result of DNA strand cleavage due to 1 O 2 generation or from DNA cross-linking, these interactions are often thought to play a role in determining the cytotoxicity of Ru complexes. For this reason, it was important to assess the covalent DNA binding (with complexes 1 and 2 ) or DNA cleavage (with complex 3 ) of the selected free Ru complexes and Ru complex-loaded PEG-ASP CNAs.…”

Section: Resultsmentioning

confidence: 99%

“…1, 3b, 3c, 4 In this manner, polypyridyl Ru complexes are similar to current Pt chemotherapeutics; however, while cisplatin primarily forms intrastrand DNA cross-links, Ru complexes similar to the ones analyzed here are believed to preferentially form interstrand DNA cross-links. 2a, 2b, 5 Based on this, the potential of photoactivatable Ru complexes is hypothesized to be greater than Pt-based therapies, as the difficulty of repairing interstrand cross-links is much higher compared to intrastrand cross-links, and it also may be possible to form cross-links between a strand of DNA and a protein, further complicating potential repair. 5b, 6 By exploiting these features, it is possible to develop light-activated Ru prodrugs for localized cancer therapy.…”

Section: Introductionmentioning

confidence: 99%

“…2a, 2b, 5 Based on this, the potential of photoactivatable Ru complexes is hypothesized to be greater than Pt-based therapies, as the difficulty of repairing interstrand cross-links is much higher compared to intrastrand cross-links, and it also may be possible to form cross-links between a strand of DNA and a protein, further complicating potential repair. 5b, 6 By exploiting these features, it is possible to develop light-activated Ru prodrugs for localized cancer therapy. A number of photoactivatable polypyridyl Ru complexes have been developed in our laboratory that bind to DNA and displayed cytotoxicity similar to cisplatin after photoactivation; however, while preliminary in vitro results have been promising, these therapeutics have not been characterized in vivo .…”

Section: Introductionmentioning

confidence: 99%

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Light-sensitive ruthenium complex-loaded cross-linked polymeric nanoassemblies for the treatment of cancer

et al. 2016

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This work focuses on improving the efficacy of photoactivatable Ru complexes for photodynamic therapy by employing cross-linked nanoassemblies (CNAs) as a delivery approach. The effects of complex photoactivation, hydrophobicity, and solution ionic strength and pH on complex loading and release from CNAs were analyzed. The cell cytotoxicity of CNA formulations was similar to free Ru complexes despite reduced or eliminated DNA interactions. The release rate and the amount of each Ru complex released (%) varied inversely with complex hydrophobicity, while the effect of solution ionic strength was dependent on complex hydrophobicity. Premature release of two photoactivatable prodrugs prior to irradiation was believed to account for higher activity in cells studies compared to DNA interaction studies; however, for photostable 1O2 generator-loaded CNAs this cannot explain the high cytotoxicity and lack of DNA interactions because release was incomplete after 48 hrs. The cause remains unclear, but among other possibilities, accelerated release in a cell culture environment may be responsible.

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Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Light-sensitive ruthenium complex-loaded cross-linked polymeric nanoassemblies for the treatment of cancer

et al. 2016

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“…At higher levels of ruthenation, the band disappeared due to the aggregation of Ru-DNA adducts which inhibited the intercalation of ethidium bromide into the DNA molecules. Recently, some photoreactive ruthenium(II) complexes have been studied as potential anticancer agents [25]. To evaluate the DNA photocleavage activities by 1 and 2, supercoiled plasmid pBIND DNA was used as a target.…”

Section: Resultsmentioning

confidence: 99%

DNA-binding properties of ruthenium(II) complexes with the bidentate ligand 5-chloro-2-(phenylazo)pyridine

Ratanaphan

Nhukeaw

Temboot

et al. 2012

Transition Met Chem

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A bidentate ligand, 5-chloro-2-(phenylazo)pyridine (Clazpy), and its two polypyridyl ruthenium(II) complexes, [Ru(Clazpy) 2 bpy]Cl 2 Á7H 2 O (1) and [Ru(Clazpy) 2 phen]Cl 2 Á8H 2 O (2), were synthesized and characterized. The DNA-binding properties of these complexes with DNA, the breast cancer susceptibility gene 1 (BRCA1), and the pBIND plasmid DNA were probed by photocleavage, electronic absorption titration, ethidium bromide quenching, and thermal denaturation. Both complexes were found to bind to the BRCA1 fragment through the intercalative mode into the base pairs of DNA, and the DNA-binding constants (K b ) for 1 and 2 were 7.0 9 10 4 M -1 and 5.1 9 10 5 M -1 , respectively. In addition, both complexes enhanced the single-stranded cleavage of the plasmid DNA. Under comparable experimental conditions, 2 cleaved DNA more effectively than 1, in a dose-response manner. The data indicated that the binding affinity of these two complexes to DNA was dependent on the aromatic planarity and hydrophobicity of the intercalative polypyridyl ligand.

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Synthesis and cytotoxicity of metal 4-methyl-8-quinolinethiolates

Lukevics

Шестакова

Домрачева

et al. 2007

Chem Heterocycl Compd

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It has been shown that the introduction of a methyl group at position 4 of the quinoline ring in metal 8-quinolinethiolates brings about a significant increase in the selectivity of their cytotoxic activity. It was found that rhodium 4-methyl-8-quinolinethiolate is 46 times less toxic than the unsubstituted 8-quinolinethiolate but with comparable toxicity towards MG-22A tumor cells (LC 50 2 µg/ml).Many organic derivatives of copper [1], ruthenium [2], rhodium [3], and palladium [4] containing a metal to sulfur bond shown antitumor activity. We have shown that the 8-quinolinethiolates of copper, cadmium, indium, antimony, bismuth, ruthenium, rhodium, palladium, osmium, iridium, and platinum show high cytotoxicity towards HT-1080 (human fibrosarcoma), MG-22A (mouse hepatoma), and B-16 (mouse melanoma) cells [5]. The highest activity to HT-1080 was shown by the iridium complex and to the MG-22A by the osmium complex. However, all of the metal 8-quinolinethiolates studied proved highly toxic towards normal NIH 3T3 mouse embryonic fibroblasts [5].The introduction of substituents in the quinoline ring allowed us to decrease the toxicity and increase the selectivity of di(8-quinolyl) disulfides [6] and also to decrease the toxicity of the analogous metal 8-quinolineselenolates through introduction of a 4-methyl group into the quinoline ring [7]. We have therefore synthesized a series of metal 4-methyl-8-quinolinethiolates 1a-g (Table 1) with the aim of decreasing the toxicity of the highly active complexes and studied their cytotoxicity on two tumour cell lines HT-1080 and MG-22A as well as on normal NIH 3T3 fibroblasts which served as a toxicity measure of the compounds (alternative method of determining LD 50 [8]). N Me S n M n+ 1 a M = Cu, b M = Ru, c M = Rh, d M = Pd, e M = Os, f M = Ir, g M = Pt; a,d,g n = 2, b, c, e, f n = 3

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₄₄ Ru Perspectives of Ruthenium Complexes in Cancer Therapy

Cited by 9 publications

References 0 publications

Light-sensitive ruthenium complex-loaded cross-linked polymeric nanoassemblies for the treatment of cancer

Light-sensitive ruthenium complex-loaded cross-linked polymeric nanoassemblies for the treatment of cancer

DNA-binding properties of ruthenium(II) complexes with the bidentate ligand 5-chloro-2-(phenylazo)pyridine

Synthesis and cytotoxicity of metal 4-methyl-8-quinolinethiolates

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44 Ru Perspectives of Ruthenium Complexes in Cancer Therapy

Cited by 9 publications

References 0 publications

Light-sensitive ruthenium complex-loaded cross-linked polymeric nanoassemblies for the treatment of cancer

Light-sensitive ruthenium complex-loaded cross-linked polymeric nanoassemblies for the treatment of cancer

DNA-binding properties of ruthenium(II) complexes with the bidentate ligand 5-chloro-2-(phenylazo)pyridine

Synthesis and cytotoxicity of metal 4-methyl-8-quinolinethiolates

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₄₄ Ru Perspectives of Ruthenium Complexes in Cancer Therapy