Dinuclear Ruthenium(II) Complexes That Induce and Stabilise G‐Quadruplex DNA

Abstract

A series of dinuclear ruthenium(II) complexes were synthesised, and the complexes were determined to be new highly selective compounds for binding to telomeric G-quadruplex DNA. The interactions of these complexes with telomeric G-quadruplex DNA were studied by using circular dichroism (CD) spectroscopy, fluorescence resonance energy transfer (FRET) melting assays, isothermal titration calorimetry (ITC) and molecular modelling. The results showed that the complexes 1, 2 and 4 induced and stabilised the formation of antiparallel G-quadruplexes of telomeric DNA in the absence of salt or in the presence of 100 mM K(+)-containing buffer. Furthermore, complexes 1 and 2 strongly bind to and effectively stabilise the telomeric G-quadruplex structure and have significant selectivity for G-quadruplex over duplex DNA. In comparison, complex 3 had a much lesser effect on the G-quadruplex, suggesting that possession of a suitably sized plane for good π-π stacking with the G-quadruplets is essential for the interaction of the dinuclear ruthenium(II) complexes with the G-quadruplex. Moreover, telomerase inhibition by the four complexes and their cellular effects were studied, and complex 1 was determined to be the most promising inhibitor of both telomerase and HeLa cell proliferation.

Microwave-assisted synthesis of polypyridyl ruthenium(ii) complexes as potential tumor-targeting inhibitors against the migration and invasion of Hela cells through G2/M phase arrest

“…The treatment of cervical cancer faces one of the most challenging problems in clinical oncology in that there are few effective treatments to block the metastasis of cervical cancer cells. [12][13][14][15] Ruthenium complexes have always been regarded as some of the most potential antitumour inhibitors owing to their decent antitumour activity [16][17][18][19][20] and low toxicity. [21][22][23][24] A number of Ru complexes have been designed and their anti-metastasis activities against various tumours have been investigated extensively.…”

Development of squaraine based G-quadruplex ligands using click chemistry

“…Such G4 forming sequences have been reported to be prevalent in genomes, such as immunoglobulin switch regions and promoter regions of oncogenes and telomere ends 4, 5 , as well as in particular RNA domains, such as the first introns, 5′- and 3′- untranslated regions, telomeric RNA 6 , and the genomic RNA of Zika virus replication 7 . Accumulating evidence has suggested that G4s play an intrinsic role in gene expression 8–14 .…”

Cover Feature: Towards the Development of Photo‐Reactive Ruthenium(II) Complexes Targeting Telomeric G‐Quadruplex DNA (Chem. Eur. J. 72/2018)

“…[21] They demonstratedt he ability of this NDI-phenolate conjugate to kill MCF7 cancer cells after irradiation.The design of new metal complexes targeting G-quadruplex DNA has attracted intense interestw ithr egard to their potential anticancer properties. [22,23] Indeed, some Pt II , [24][25][26][27][28] Ni II , [29][30][31] Ru II , [32][33][34] and Ir III complexes [35][36][37] have shown good affinity and selectivity towards G4s. In comparison to organic compounds, metal complexeshave many advantages, such as anet positive charge,t unable geometry,a nd, most interestingly,s ome of them display potentially useful photochemical properties.…”