Targeting Human Telomeric G-Quadruplex DNA and Inhibition of Telomerase Activity With [(dmb)2Ru(obip)Ru(dmb)2]4+

Shi, Shuo; Gao, Shane; Cao, Tongcheng; Liu, Jie; Gao, Xing; Hao, Jian Guo; Lv, Chunyan; Huang, Hailiang; Xu, Jun; Yao, Tianming

doi:10.1371/journal.pone.0084419

Cited by 16 publications

(6 citation statements)

References 64 publications

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“…[26] Therefore, the Ru II complex may only bind as an end-capping molecule on either lateral loop faces, similar to other reports of Ru II polypyridyl complexes with duplex and Gquadruplex DNA. [10b, 26,30] In this type of binding mode, the dmdppz or dmdppz-Br ligand would only interactw ith one set of guanosines,r ather than two sets in an intercalating binding mode,a nd facilitatethe melting process through atriplex.…”

Section: Resultsmentioning

confidence: 99%

Ruthenium Complex “Light Switches” that are Selective for Different G‐Quadruplex Structures

Wachter

Moyá

Parkin

et al. 2015

Chemistry A European J

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Recognition and regulation of G-quadruplex nucleic acid structures is an important goal for the development of chemical tools and medicinal agents. The addition of a bromo substituent to the dipyridylphenazine (dppz) ligands in the photophysical “light switch”, [Ru(bpy)2dppz]2+, and the photochemical “light switch”, [Ru(bpy)2dmdppz]2+, creates compounds with increased selectivity for an intermolecular parallel G-quadruplex and the mixed-hybrid G-quadruplex, respectively. When [Ru(bpy)2dppz-Br]2+ and [Ru(bpy)2dmdppz-Br]2+ are incubated with the G-quadruplexes, they have a stabilizing effect on the DNA structures. Activation of [Ru(bpy)2dmdppz-Br]2+ with light results in covalent adduct formation with the DNA. These complexes demonstrate that subtle chemical modifications of RuII complexes can alter G-quadruplex selectivity, and could be useful for the rational design of in vivo G-quadruplex probes.

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Section: Resultsmentioning

confidence: 99%

Ruthenium Complex “Light Switches” that are Selective for Different G‐Quadruplex Structures

Wachter

Moyá

Parkin

et al. 2015

Chemistry A European J

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“…With increasing interest in the new antitumor targets G4 and telomerase, a number of ruthenium(II/III)-based anticancer agents targeting G4 and telomerase such as [Ru(bpy) 2 (tip)] 2+ and [Ru(phen) 2 (tip)] 2+ , [(C 6 H 6 )Ru( o -ClPIP)Cl]Cl, [Ru(bpy)(biim)], [Ru(phen)(biim)], and [Ru( p -mopip)(biim)], [Ru(bpy)(pedppz)] and [Ru(bpy)(pemitatp)], [Ru(bpy) 2 (ptpn)] 2+ and [Ru(pehn) 2 (ptpn)] 2+ , [(η 6 -arene)Ru(en)Cl] + , [Ru(ip) 3 ](ClO 4 ) 2 and [Ru(pip) 3 ](ClO 4 ) 2 , and [(dmb) 2 Ru(obip)Ru(dmb) 2 ] 4+ , have been reported. However, only a few chiral anticancer ruthenium complexes, such as ruthenium(II) arene PTS (RAPTA) complexes, Λ-[Ru(phen) 2 ( p -MOPIP)] 2+ and Δ-[Ru(phen) 2 ( p -MOPIP)] 2+ , [{Ru(phen) 2 } 2 tpphz] 4+ , Λ-[Ru(phen) 2 ( p -HPIP)] 2+ , and Δ-[Ru(phen) 2 ( p -HPIP)] 2+ , which display inhibitory effects on telomerase activity by stabilization of G4-DNA, have been developed.…”

Section: Introductionmentioning

confidence: 99%

Water-Soluble Ruthenium(II) Complexes with Chiral 4-(2,3-Dihydroxypropyl)-formamide Oxoaporphine (FOA): In Vitro and in Vivo Anticancer Activity by Stabilization of G-Quadruplex DNA, Inhibition of Telomerase Activity, and Induction of Tumor Cell Apoptosis

et al. 2015

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Three water-soluble ruthenium(II) complexes with chiral 4-(2,3-dihydroxypropyl)-formamide oxoaporphine (FOA) were synthesized and characterized. It was found that these ruthenium(II) complexes exhibited considerable in vitro anticancer activities and that they were the effective stabilizers of telomeric and G-quadruplex-DNA (G4-DNA) in promoter of c-myc, which acted as a telomerase inhibitor targeting G4-DNA and induced cell senescence and apoptosis. Interestingly, the in vitro anticancer activity of 6 (LC-003) was higher than those of 4 (LC-001) and 5 (LC-002), more selective for BEL-7404 cells than for normal HL-7702 cells, and preferred to activate caspases-3/9. The different biological behaviors of the ruthenium complexes could be correlated with the chiral nature of 4-(2,3-dihydroxypropyl)-formamide oxoaporphine. More significantly, 6 exhibited effective inhibitory on tumor growth in BEL-7402 xenograft mouse model and higher in vivo safety than cisplatin. These mechanistic insights indicate that 6 displays low toxicity and can be a novel anticancer drug candidate.

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“…No in-depth study has been carried out on the interaction of other dinuclear ruthenium(II) complexes bearing a bridging imidazo-phen ligand ( bpibp , pyip , bpip , bpip-CH 3 -OH , bpip-Cz, and tpipib ) with G-quadruplexes, but they have been investigated as potential anti-cancer drugs due to their ability to stabilize G-quadruplex structures [ 263 , 264 , 265 ]. Two examples of trinuclear ruthenium(II) complexes ([{Ru(bpy) 2 } 3 ( tpbip )]6 + and [{Ru(bpy) 2 } 3 ( tptaip )]6 + ) ( Figure 29 ) have also been studied for the same purpose [ 266 ].…”

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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Targeting Human Telomeric G-Quadruplex DNA and Inhibition of Telomerase Activity With [(dmb)2Ru(obip)Ru(dmb)2]4+

Cited by 16 publications

References 64 publications

Ruthenium Complex “Light Switches” that are Selective for Different G‐Quadruplex Structures

Ruthenium Complex “Light Switches” that are Selective for Different G‐Quadruplex Structures

Water-Soluble Ruthenium(II) Complexes with Chiral 4-(2,3-Dihydroxypropyl)-formamide Oxoaporphine (FOA): In Vitro and in Vivo Anticancer Activity by Stabilization of G-Quadruplex DNA, Inhibition of Telomerase Activity, and Induction of Tumor Cell Apoptosis

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

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