DNA-binding, topoisomerases I and II inhibition and in vitro cytotoxicity of ruthenium(II) polypyridyl complexes: [Ru(dppz)2L]2+ (L = dppz-11-CO2Me and dppz)

•Two Ru(II) complexes have been synthesized and characterized.•The two complexes bound to CT-DNA via intercalation with different affinities.•Both complexes were dual inhibitors of topoisomerases I and II.•Both complexes exhibited antitumor activity against the selected tumor cells.

Two ruthenium(II) polypyridyl complexes, [Ru(dppz)2dppz-11-CO2Me](ClO4)2 (Ru1) and [Ru(dppz)3](ClO4)2 (Ru2), have been synthesized and characterized. The spectral characteristics of Ru1 and Ru2 were investigated by fluorescence spectroscopy and revealed that both complexes were sensitive to solvent polarity. The binding properties of the two complexes towards calf-thymus DNA (CT-DNA) have been investigated by different spectrophotometric methods and viscosity measurements, indicating that both complexes bind to CT-DNA by means of intercalation, but with different binding affinities. Topoisomerase inhibition and DNA strand passage assay demonstrates that the two complexes are dual inhibitors of topoisomerases I and IIa. On the other hand, the cytotoxicity of both complexes has been evaluated by MTT assays and Giemsa staining experiments. The main results reveal that the ester functional group has a significant effect on the DNA-binding affinities and topoisomerases inhibition effects of Ru1 and Ru2, and further advance our knowledge on the DNA-binding and topoisomerase inhibition by Ru(II) complexes.

Graphical abstractRu1 and Ru2 can intercalate into DNA base pairs with different binding constants. The enzyme inhibition assay indicates that both complexes are dual inhibitors of topoisomerases I and IIa, but with different inhibitory effect. Cytotoxicity evaluation in vitro shows that both complexes displayed moderate antitumor activity against the selected tumor cell lines and can induce the apoptosis of HepG2 cells. The here reported results indicate that the ester functional group can modulate their DNA-binding affinities and topoisomerases inhibition effects of Ru1 and Ru2.Figure optionsDownload full-size imageDownload as PowerPoint slide