Towards the Development of Photo-Reactive Ruthenium(II) Complexes Targeting Telomeric G-Quadruplex DNA.

Weynand, Justin;Diman, Aurélie;Abraham, Michaël;Marcélis, Lionel;Elias, Benjamin;et.al.
(2018) Chemistry: A European Journal — Vol. 24, n° 72, p. 19216-19227 (2018)

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  • Weynand, JustinUCLouvain
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  • Diman, Aurélie
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  • Abraham, MichaëlUCLouvain
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  • Marcélis, Lionelorcid-logoUCLouvain
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  • Defrancq, EricUCLouvain
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Abstract
The design and characterization of new ruthenium(II) complexes aimed at targeting G-quadruplex DNA is reported. Importantly, these complexes are based on oxidizing 1,4,5,8-tetraazaphenanthrene (TAP) ancillary ligands known to favour photo-induced electron transfer (PET) with DNA. The photochemistry of complexes 1-4 has been studied by classical methods, which revealed two of them to be capable of photo-abstracting an electron from guanine. From studies of the interactions with DNA through luminescence, circular dichroism, bio-layer interferometry, and surface plasmon resonance experiments, we have demonstrated the selectivity of these complexes for telomeric G-quadruplex DNA over duplex DNA. Preliminary biological studies of these complexes have been performed: two of them showed remarkable photo-cytotoxicity towards telomerase-negative U2OS osteosarcoma cells, whereas very low mortality was observed in the dark at the same photo-drug concentration.
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Citations

Weynand, J., Diman, A., Abraham, M., Marcélis, L., Jamet, H., Decottignies, A., Dejeu, J., Defrancq, E., & Elias, B. (2018). Towards the Development of Photo-Reactive Ruthenium(II) Complexes Targeting Telomeric G-Quadruplex DNA. Chemistry: A European Journal, 24(72), 19216-19227. https://doi.org/10.1002/chem.201804771 (Original work published 2018)