G-quadruplex and duplex DNA binding studies of novel Ruthenium(II) complexes containing ascididemin ligands

Wumaier, Maierhaba; Shi, Jingjing; Yao, Tianming; Hu, Xiaochun; Gao, Ruru; Shi, Shuo

doi:10.1016/j.jinorgbio.2019.03.021

Cited by 17 publications

(6 citation statements)

References 77 publications

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“…Among these complexes, metal complexes have unique characteristics of specific base-recognizing ability and stable fluorescence. For examples, Rhodium complexes bearing the sterically expansive 5,6-chrysene diimine (chrysi) ligand could preferentially target thermodynamically destabilized mismatches [31,32],and several ruthenium complexes can be used as luminescent light switches for single-base mismatches of dsDNA [33,34]. Therefore, in this study we use the ruthenium complexes to investigate their selective toxicity to glioma cells.…”

Section: Discussionmentioning

confidence: 99%

Discovery of a Ruthenium Complex for the Theranosis of Glioma through Targeting the Mitochondrial DNA with Bioinformatic Methods

Zhang

Jin

et al. 2019

IJMS

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Glioma is the most aggressive and lethal brain tumor in humans. Mutations of mitochondrial DNA (mtDNA) are commonly found in tumor cells and are closely associated with tumorigenesis and progress. However, glioma-specific inhibitors that reflect the unique feature of tumor cells are rare. Here we uncover RC-7, a ruthenium complex with strong red fluorescence, could bind with glioma mtDNA and then inhibited the growth of human glioma cells but not that of neuronal cells, liver, or endothelial cells. RC-7 significantly reduced energy production and increased the oxidative stress in the glioma cells. Administration of RC-7 into mice not only could be observed in the glioma mass of brain by fluorescence imaging, but also obviously prevented the growth of xenograft glioma and prolonged mouse survival days. The findings suggested the theranostic application of a novel type of complex through targeting the tumor mtDNA.

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Section: Discussionmentioning

confidence: 99%

Discovery of a Ruthenium Complex for the Theranosis of Glioma through Targeting the Mitochondrial DNA with Bioinformatic Methods

Zhang

Jin

et al. 2019

IJMS

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“…However, with the introduction of the F atom in the terminal benzene ring at the para-position, the complex displayed an obvious hypochromic effect (7.1%) with a binding energy of 6.4 × 10 5 M −1 ( Figure S22 ). These data are comparable with that of arene ruthenium complexes [( η 6 -C 6 H 6 )RuCl(pmpzdpm)] (4.29 × 10 5 M −1 ) and [( η 6 -C 10 H 14 )RuCl(pmpzdpm)] (1.79 × 10 6 M −1 ) (pmpzdpm = 5-(2-pyrimidylpiperazine)phenyldipyrromethane) [ 18 ] and [Ru(bpy) 2 ASC] 2+ (2.78 × 10 6 M −1 ) (ACS = ascididemin) [ 19 ].…”

Section: Resultsmentioning

confidence: 99%

Arene Ru(II) Complexes with Difluorinated Ligands Act as Potential Inducers of S-Phase Arrest via the Stabilization of c-myc G-Quadruplex DNA

et al. 2022

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Here, a series of half-sandwich arene Ru(II) complexes with difluorinated ligands [Ru(η6-arene)(L)Cl] (L1 = 2-(2,3-difluorophenyl)imidazole[4,5f][1,10]-phenanthroline; L2 = 2-(2,4-difluorophenyl)imidazole[4,5f][1,10]-phenanthroline; arene = benzene, toluene, and p-cymene) were synthesized and characterized. Molecular docking analysis showed that these complexes bind to c-myc G-quadruplex DNA through either groove binding or π–π stacking, and the relative difluorinated site in the main ligand plays a role in regulating the binding mode. The binding behavior of these complexes with c-myc G-quadruplex DNA was evaluated using ultraviolet–visible spectroscopy, fluorescence intercalator displacement assay, fluorescence resonance energy transfer melting assay, and polymerase chain reaction. The comprehensive analysis indicated that complex 1 exhibited a better affinity and stability in relation to c-myc G-quadruplex DNA with a DC50 of 6.6 μM and ΔTm values of 13.09 °C, than other molecules. Further activity evaluation results displayed that this class of complexes can also inhibit the growth of various tumor cells, especially complexes 3 and 6, which exhibited a better inhibitory effect against human U87 glioblastoma cells (51.61 and 23.75 μM) than other complexes, even superior to cisplatin (32.59 μM). Owing to a befitting lipophilicity associated with the high intake of drugs by tumor cells, complexes 3 and 6 had favorable lipid-water partition coefficients of −0.6615 and −0.8077, respectively. Moreover, it was found that complex 6 suppressed the proliferation of U87 cells mainly through an induced obvious S phase arrest and slight apoptosis, which may have resulted from the stabilization of c-myc G-quadruplex DNA to block the transcription and expression of c-myc. In brief, these types of arene Ru(II) complexes with difluorinated ligands can be developed as potential inducers of S-phase arrest and apoptosis through the binding and stabilization of c-myc G-quadruplex DNA, and could be used in clinical applications in the future.

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“…Two biologically active molecules ( ASC (Ascididemin) and Emodin ) have also been used to form the [Ru(L) 2 ( ASC )] 2+ (L = bpy, phen or dpq) and [Ru(bpy) 2 ( emodin )] 2+ ( Figure 23 ) complexes in order to combine the cytotoxic activity of the free ligands with the high binding affinity of ruthenium(II) complexes towards G-quadruplexes [ 247 , 248 ].…”

Section: Interactions Of Ruthenium(ii) Complexes With G-quadruplexesmentioning

confidence: 99%

Ruthenium(II) Polypyridyl Complexes and Their Use as Probes and Photoreactive Agents for G-quadruplexes Labelling

et al. 2022

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Due to their optical and electrochemical properties, ruthenium(II) polypyridyl complexes have been used in a wide array of applications. Since the discovery of the light-switch ON effect of [Ru(bpy)2dppz]2+ when interacting with DNA, the design of new Ru(II) complexes as light-up probes for specific regions of DNA has been intensively explored. Amongst them, G-quadruplexes (G4s) are of particular interest. These structures formed by guanine-rich parts of DNA and RNA may be associated with a wide range of biological events. However, locating them and understanding their implications in biological pathways has proven challenging. Elegant approaches to tackle this challenge relies on the use of photoprobes capable of marking, reversibly or irreversibly, these G4s. Indeed, Ru(II) complexes containing ancillary π-deficient TAP ligands can create a covalently linked adduct with G4s after a photoinduced electron transfer from a guanine residue to the excited complex. Through careful design of the ligands, high selectivity of interaction with G4 structures can be achieved. This allows the creation of specific Ru(II) light-up probes and photoreactive agents for G4 labelling, which is at the core of this review composed of an introduction dedicated to a brief description of G-quadruplex structures and two main sections. The first one will provide a general picture of ligands and metal complexes interacting with G4s. The second one will focus on an exhaustive and comprehensive overview of the interactions and (photo)reactions of Ru(II) complexes with G4s.

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G-quadruplex and duplex DNA binding studies of novel Ruthenium(II) complexes containing ascididemin ligands

Cited by 17 publications

References 77 publications

Discovery of a Ruthenium Complex for the Theranosis of Glioma through Targeting the Mitochondrial DNA with Bioinformatic Methods

Discovery of a Ruthenium Complex for the Theranosis of Glioma through Targeting the Mitochondrial DNA with Bioinformatic Methods

Arene Ru(II) Complexes with Difluorinated Ligands Act as Potential Inducers of S-Phase Arrest via the Stabilization of c-myc G-Quadruplex DNA

Ruthenium(II) Polypyridyl Complexes and Their Use as Probes and Photoreactive Agents for G-quadruplexes Labelling

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