期刊
CHEMISTRY-A EUROPEAN JOURNAL
卷 24, 期 72, 页码 19216-19227出版社
WILEY-V C H VERLAG GMBH
DOI: 10.1002/chem.201804771
关键词
DNA structures; G-quadruplexes; photocytotoxicity; photo-electron transfer; ruthenium complexes
资金
- Fonds National pour la Recherche Scientifique (F.R.S.-FNRS)
- Fonds pour la Formation a la Recherche dans l'Industrie et dans l'Agriculture (F.R.I.A.)
- Region Wallonne
- Universite catholique de Louvain (UCLouvain)
- Agence National de la Recherche [ANR-12-BSV8-0008-04, ANR-16-CE11-0006-01]
- Labex ARCANE [ANR-11-LABX-0003-01]
- Region Auvergne-Rhone-Alpes
- NanoBio-ICMG platforms [FR 2607]
- Agence Nationale de la Recherche (ANR) [ANR-16-CE11-0006, ANR-12-BSV8-0008] Funding Source: Agence Nationale de la Recherche (ANR)
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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