Flexible RuII Schiff base complexes: G‐quadruplex DNA binding and photo‐induced cancer cell death
| Autor: | Eric Defrancq, Hugues Bonnet, Martin Gillard, Justin Weynand, Benjamin Elias, Frédérique Loiseau, Anabelle Decottignies, Jérôme Dejeu |
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| Přispěvatelé: | UCL - SST/IMCN/MOST - Molecular Chemistry, Materials and Catalysis, UCL - SSS/DDUV/GEPI - Epigénétique, Institut de la matière condensée et des nanosciences / Institute of Condensed Matter and Nanosciences (IMCN), Université Catholique de Louvain = Catholic University of Louvain (UCL), Département de Chimie Moléculaire - Ingéniérie et Intéractions BioMoléculaires (DCM - I2BM), Département de Chimie Moléculaire (DCM), Université Grenoble Alpes (UGA)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Département de Chimie Moléculaire - Chimie Inorganique Redox Biomimétique (DCM - CIRE ) |
| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
Circular dichroism
[SDV.CAN]Life Sciences [q-bio]/Cancer [CHIM.INOR]Chemical Sciences/Inorganic chemistry 010402 general chemistry 01 natural sciences Catalysis chemistry.chemical_compound Schiff base ruthenium complexes Molecule Moiety [CHIM]Chemical Sciences Bimetallic strip ComputingMilieux_MISCELLANEOUS 010405 organic chemistry Ligand Photo-cytotoxicity Organic Chemistry General Chemistry Combinatorial chemistry 3. Good health 0104 chemical sciences [CHIM.THEO]Chemical Sciences/Theoretical and/or physical chemistry G-quadruplex DNA chemistry Bio-layer interferometry Steady state (chemistry) DNA |
| Zdroj: | Chemistry – A European Journal, (2020) Chemistry-A European Journal Chemistry-A European Journal, Wiley-VCH Verlag, In press, ⟨10.1002/chem.202001409⟩ |
| ISSN: | 0947-6539 1521-3765 |
| Popis: | A series of new RuII Schiff base complexes built on the salphen moiety has been prepared. This includes four flexible monometallic RuII compounds and six rigid bimetallic analogues that contain NiII , PdII or PtII cations into the salphen complexation site. Steady state luminescence titrations illustrated the capacity of the compounds to photoprobe G-quadruplex (G4) DNA. Moreover, the vast array of the Schiff base structural changes allowed to extensively assess the influence of the ligand surface, flexibility and charge on the interaction of the compounds with G4 DNA. This was achieved thanks to circular dichroism melting assays and bio-layer interferometry studies that pointed up high affinities along with good selectivities of RuII Schiff base complexes for G4 DNA. In cellulo studies were carried out with the most promising compounds. Cellular uptake with location of the compounds in the nucleus as well as in the nucleolus was observed. Cell viability experiments were performed with U2OS osteosarcoma cells in the dark and under light irradiation which allowed the measurements of IC50 values and photoindexes. They showed the substantial role played by light irradiation in the activity of the drugs in addition to the low cytotoxicity of the molecules in the dark. Altogether, the reported results emphasize the promising properties of RuII Schiff base complexes as a new class of candidates for developing potential G4 DNA targeting diagnostic or therapeutic compounds. |
| Databáze: | OpenAIRE |
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