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Flexible Ru II Schiff Base Complexes: G‐Quadruplex DNA Binding and Photo‐Induced Cancer Cell Death
Author(s) -
Gillard Martin,
Weynand Justin,
Bonnet Hugues,
Loiseau Frédérique,
Decottignies Anabelle,
Dejeu Jérôme,
Defrancq Eric,
Elias Benjamin
Publication year - 2020
Publication title -
chemistry – a european journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.687
H-Index - 242
eISSN - 1521-3765
pISSN - 0947-6539
DOI - 10.1002/chem.202001409
Subject(s) - schiff base , chemistry , ligand (biochemistry) , dna , titration , luminescence , stereochemistry , crystallography , photochemistry , inorganic chemistry , materials science , biochemistry , receptor , optoelectronics
A series of new Ru II Schiff base complexes built on the salphen moiety has been prepared. This includes four flexible monometallic Ru II compounds and six rigid bimetallic analogues that contain Ni II , Pd II or Pt II 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 Ru II 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 IC 50 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 Ru II Schiff base complexes as a new class of candidates for developing potential G4 DNA targeting diagnostic or therapeutic compounds.