Study of Photo-Reactive Ruthenium(II) Complexes Targeting Telomeric G-Quadruplex DNA
(2018) Merck Organic Chemistry Symposium 2018 — Location: Blankenberge (6.December.2018)
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- Abstract
- Since the discovery of the anticancer properties of cisplatin, using new metals has progressively gained interest for the development of new therapeutic agents [1,2]. Among them, polyazaaromatic complexes of Ru(II) have shown interesting photochemical and photophysical properties. Indeed, upon light irradiation, the oxidation and reduction potential of these compounds are enhanced and for some of them, photocleavage and/or photoadduct formation with DNA have been demonstrated [3]. In this context, we aim at designing new photo-oxidizing complexes of Ru(II) complexes for the targeting of G-quadruplex DNA. G-quadruplex (G4) consist in secondary structures adopted by guanines-rich nucleic acids. These structures are formed through the stacking of guanine tetrads (G-quartet), the latter resulting from the coplanar arrangement of four guanines. They have been found in the telomeres where they appear to play crucial biological roles. Therefore, designing ligands able to selectively target G-quadruplex versus duplex DNA is of great interest. We report therein on the synthesis of new photo-oxidizing ruthenium(II) complexes [4]. They are able to photo-induce oxidative damage to telomeric G-quadruplex DNA through photo-induced electron transfer (PET) with guanine. The affinity and selectivity for G-quadruplex DNA have been evidenced thanks to steady-state luminescence studies, BLI and molecular modelling. Finally, we demonstrated the cell internalization and the photo-cytotoxicity towards human osteosarcoma cells. References [1] B. Rosenberg et al., Nature 2017, 222, 385-386. [2] MR. Gill et al., Chem. Soc. Rev. 2012, 41, 3179-3192. [3] B. Elias et al., Coordination Chem. Review. 2006, 1627-1641. [4] J. Weynand et al., Chem. Eur. J. 2018, in press.
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Weynand, J., Diman, A., Abraham, M., Marcélis, L., Jamet, H., Decottignies, A., Dejeu, J., Defrancq, E., & Elias, B. (2018). Study of Photo-Reactive Ruthenium(II) Complexes Targeting Telomeric G-Quadruplex DNA. Merck Organic Chemistry Symposium 2018, Blankenberge. https://hdl.handle.net/2078.5/59855