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Synthesis of 1,10-Phenanthroline-2,9-bistriazoles: Evaluation as G-Quadruplex Binders and Anti-Tumor Activity. | LitMetric
Novel 1,10-phenanthroline-2,9-bistriazoles derivatives have been synthesized by copper-catalyzed azide/alkyne cycloaddition reactions and assessed for their ability to bind and stabilize G-quadruplex (G4) structures. Ten novel compounds were evaluated using Förster resonance energy transfer (FRET) melting, circular dichroism (CD), and fluorescence spectroscopy on several G4 sequences. Biophysical characterization led to the identification of compounds 4 a, 4 b, and 5 b as good G4 ligands of KRAS G4 sequences. The impact on cell viability of all derivatives was also assessed, revealing weak effects. However, compound 2 a exhibited cytotoxicity activity on A549 and H1299 cancer cells and low cytotoxicity towards MRC-5 non-malignant cells MRC-5 not connected with its G4-binding ability. Flow cytometry showed that 2 a induced a cell viability decrease in S and G2/M phases for A549 and H1299; thus, more studies should be performed to explore the proteins involved in cell cycle regulation.
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