Ruthenium coordination compounds of biological and biomedical significance. DNA binding agents

Brabec, Viktor; Kašpárková, Jana

doi:10.1016/j.ccr.2018.07.012

Cited by 145 publications

(90 citation statements)

References 131 publications

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“…The strength of the positive signal at 265 nm decreased by 87.4% for Pu27 DNA and 71.2% for Pu22 DNA, and simultaneously an obvious negative induce CD signal at a wavelength of 295 nm appeared both for Pu27 and Pu22 DNA. These results further confirmed that the complex can interact with c-myc DNA tightly through groove mode, which is similar to the Pu27 binding behavior of [(η 6 For validating the binding stoichiometry of the ruthenium complex with c-myc quadruplex DNA, a continuous variation analysis was used. Fixed the total concentration of ruthenium complex and c-myc G-quadruplex DNA, the fluorescence intensities of the mixed solutions of complex and c-myc DNA with different concentration ratios are different.…”

Section: Binding Behavior Of Ruthenium Complex With C-myc G-quadruplesupporting

confidence: 74%

“…Ruthenium(II) complexes have attracted extensively attentions as potential alternative drugs for cis-platin in metal-based cancer therapy, due to their excellent binding affinity and luminescene-probe behavior for DNA [1-4], high selectivity to tumor cells and relatively low toxicity toward human normal cells [5][6][7][8]. Research of the last few decades by Chao et al revealed that binding of ruthenium(II) complexes with G-quadruplex DNA plays an important role in their inhibition of tumor cell growth [9][10][11].…”

Section: Introductionmentioning

confidence: 99%

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Induction of C-Myc G-Quadruplex Dna and Cytotoxicity of a Calix[]arene-Containing Binuclear Ruthenium(ii) Complex

Wang

Yan

et al. 2019

J. Chil. Chem. Soc.

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Herein, a binuclear ruthenium(II) complex modified by calix[4]arene group has been prepared. The complex as potential inducer and stabilizer of c-myc Gquadruplex DNA and antitumor reagent were studied. Observations revealed that the complex could bind to c-myc Pu27 and Pu22 DNA strongly with constants of 1.18 × 10 7 (Pu27) and 4.13 × 10 6 M-1 (Pu22) via groove mode as determined from absorption and luminescence titrations, as well as CD spectra. Results of continuous variation analysis confirmed that the complex interacted with c-myc G-quadruplex DNA through a 1:1 binding stoichiometry. As verified by PCR-stop assay, the replication of c-myc DNA was effectively blocked by the complex with the complete inhibition at the complex concentration of 4.0 μM both for Pu27 and Pu22, suggesting that the complex could efficiently induce the formation of c-myc G-quadruplex DNA. The appearance of blue TMB solution in the visual experiment also proved that the sequences of Pu27 and Pu22 could fold into G-quadruplex under the induction of the complex. Nevertheless, the complex was found to exhibit weak stabilization ability on c-myc G-quadruplex DNA according to FRET assay, which increased the melting point of c-myc DNA only 3-3.5 °C. The experiments on Topoisomerase inhibition and cytotoxicity of the complex showed that it acted as an inhibitor of TopoI and exhibited moderate anticancer activity against MCF-7 and Huh-7 tumor cells.

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Section: Binding Behavior Of Ruthenium Complex With C-myc G-quadruplesupporting

confidence: 74%

Section: Introductionmentioning

confidence: 99%

Induction of C-Myc G-Quadruplex Dna and Cytotoxicity of a Calix[]arene-Containing Binuclear Ruthenium(ii) Complex

Wang

Yan

et al. 2019

J. Chil. Chem. Soc.

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“…The spatial discrimination was identified as an element of the precise geometric positioning of introduced photosensitizer relative to the redox cofactors and the additional prerequisite of the fast electron transfer between photosensitizer and heme cofactor. In view of the growing applications of Ru(II) polypyridyl complexes as photosensitive groups (Brabec and Kasparkova 2018;Lam et al 2016;Mital and Ziora 2018), the results depicted here are valuable for understanding their interactions with protein matrices and enhance our ability to design controlled electron transfer pathways in photo-activated biohybrids molecules.…”

Section: Introductionmentioning

confidence: 97%

Examination of abiotic cofactor assembly in photosynthetic biomimetics: site-specific stereoselectivity in the conjugation of a ruthenium(II) tris(bipyridine) photosensitizer to a multi-heme protein

et al. 2020

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To understand design principles for assembling photosynthetic biohybrids that incorporate precisely-controlled sites for electron injection into redox enzyme cofactor arrays, we investigated the influence of chirality in assembly of the photosensitizer ruthenium(II)bis(2,2′-bipyridine)(4-bromomethyl-4′-methyl-2,2′-bipyridine), Ru(bpy) 2 (Br-bpy), when covalently conjugated to cysteine residues introduced by site-directed mutagenesis in the triheme periplasmic cytochrome A (PpcA) as a model biohybrid system. For two investigated conjugates that show ultrafast electron transfer, A23C-Ru and K29C-Ru, analysis by circular dichroism spectroscopy, CD, demonstrated site-specific chiral discrimination as a factor emerging from the close association between [Ru(bpy) 3 ] 2+ and heme cofactors. CD analysis showed the A23C-Ru and K29C-Ru conjugates to have distinct, but opposite, stereoselectivity for the Λ and Δ-Ru(bpy) 2 (Br-bpy) enantiomers, with enantiomeric excesses of 33.1% and 65.6%, respectively. In contrast, Ru(bpy) 2 (Br-bpy) conjugation to a protein site with high flexibility, represented by the E39C-Ru construct, exhibited a nearly negligible chiral selectivity, measured by an enantiomeric excess of 4.2% for the Λ enantiomer. Molecular dynamics simulations showed that site-specific stereoselectivity reflects steric constraints at the conjugating sites and that a high degree of chiral selectivity correlates to reduced structural disorder for [Ru(bpy) 3 ] 2+ in the linked assembly. This work identifies chiral discrimination as means to achieve site-specific, precise geometric positioning of introduced photosensitizers relative to the heme cofactors in manner that mimics the tuning of cofactors in photosynthesis.

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“…The versatility of such compounds rely on the possibility to vary the nature of the substituent group in the intercalative ligand, modifying the configuration and electron density distribution of the metal center, allowing to obtain different DNA binding affinities and photo‐cleavage properties. Following this approach, a considerable number of compounds have been reported, including [Ru(bpy) 2 (dppz)] 2+ and [Ru(bpy) 2 (pip)] 2+ (dppz=dipyridophenazine, pip=2‐phenylimidazo[4,5‐f][1,10]phenanthroline), which feature interesting properties as site‐specific luminescent DNA binding agents and abilities to stall the DNA replication of cancer cells as well . However, some critical disadvantages, such as the short lifetime of triplet excited state that reduces the 1 O 2 quantum yield, the low DNA cleavage activity and the poor solubility in physiological media, may represent a serious limit for their further development as PSs in clinical trials .…”

Section: Introductionmentioning

confidence: 99%

“…Following this approach,aconsiderable number of compounds have been reported, including [Ru(bpy) 2 (dppz)] 2 + and [Ru(bpy) 2 (pip)] 2 + (dppz = dipyridophenazine, pip = 2-phenylimidazo[4,5-f] [1,10]phenanthroline), which feature interesting properties as site-specific luminescentD NA binding agentsa nd abilitiest o stall the DNA replication of cancerc ells as well. [13,14] However, some critical disadvantages, such as the short lifetimeo ft riplet excited state that reduces the 1 O 2 quantum yield, the low DNA cleavage activity and the poor solubility in physiological media, may represent as erious limit for their further development as PSs in clinicalt rials. [15] In this context, Ru-polypyridyl complexes featuring charged polyamino chains appended to the heteroaromatic units represent an appealing choice, although, to the best of our knowledge,t hey have not been largely investigated as PDT photosensitizer.…”

Section: Introductionmentioning

confidence: 99%

Highly Charged Ruthenium(II) Polypyridyl Complexes as Effective Photosensitizer in Photodynamic Therapy

Conti

Bencini

Ferrante

et al. 2019

Chemistry A European J

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A comparative study between two novel, highly water soluble, ruthenium(II) polypyridyl complexes, [Ru(phen)2L′] and [Ru(phen)2Cu(II)L′] (L and L‐CuII), containing the polyaazamacrocyclic unit 4,4′‐(2,5,8,11,14‐pentaaza[15])‐2,2′‐bipyridilophane (L′), is herein reported. L and L‐CuII interact with calf‐thymus DNA and efficiently cleave DNA plasmid when light‐activated. They also possess great penetration abilities and photo‐induced biological activities, evaluated on an A375 human melanoma cell line, with L‐CuII being the most effective. Our study highlights the key role of the Fenton active CuII center within the macrocycle framework, that would play a synergistic role with light activation in the formation of cytotoxic ROS species. Based on these results, an optimal design of RuII polypyridyl systems featuring specific CuII‐chelating polyamine units could represent a suitable strategy for the development of novel and effective photosensitizers in photodynamic therapy.

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Ruthenium coordination compounds of biological and biomedical significance. DNA binding agents

Cited by 145 publications

References 131 publications

Induction of C-Myc G-Quadruplex Dna and Cytotoxicity of a Calix[]arene-Containing Binuclear Ruthenium(ii) Complex

Induction of C-Myc G-Quadruplex Dna and Cytotoxicity of a Calix[]arene-Containing Binuclear Ruthenium(ii) Complex

Examination of abiotic cofactor assembly in photosynthetic biomimetics: site-specific stereoselectivity in the conjugation of a ruthenium(II) tris(bipyridine) photosensitizer to a multi-heme protein

Highly Charged Ruthenium(II) Polypyridyl Complexes as Effective Photosensitizer in Photodynamic Therapy

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