Cellular uptake, cytotoxicity, apoptosis, DNA-binding, photocleavage and molecular docking studies of ruthenium(II) polypyridyl complexes

• DNA binding studies, Ru(II) complexes intercalate between CT-DNA base pairs.
• Cellular uptake studies showed effective shrinkage of HeLa cell lines.
• Apoptosis results reveal good percentage in late apoptosis region.

Three new mononuclear [Ru (phen)2 ptip]2+ (1), [Ru (bpy)2 ptip]2+ (2) and [Ru (dmb)2 ptip]2+ (3) [ptip = (2-(5-phenylthiophen-2-yl)-1H-imidazo[4, 5-f][1,10 phenanthroline, phen = 1, 10 phenanthroline, bpy = 2, 2′ bipyridine, dmb = 4, 4′-dimethyl 2, 2′ bipyridine] complexes were synthesized and characterised by elemental analysis, IR, NMR and Mass spectra. The DNA-binding behaviours were investigated by electronic absorption titration, luminescence spectra, viscosity measurements and photo-activated cleavage. The DNA-binding constants Kb of complexes 1, 2 and 3 were determined to be 7.0 (±0.06) × 105, 3.87 (±0.04) × 105, 2.79 (±0.07) × 105 respectively. The results showed that these complexes interact with CT-DNA by intercalative mode. Cell viability experiments indicated that the Ru(II) complex showed significant dose-dependent cytotoxicity to HeLa tumour cell lines. Further flow cytometry experiments showed that the cytotoxic Ru(II) complex induced apoptosis of HeLa tumour cell lines. Our data demonstrated that the Ru(II) polypyridyl complex binds to DNA and thereby induces apoptosis in tumor cells, suggesting that anti-tumor activity of the Ru(II) complex could be related to its interaction with DNA. The molecular dynamic simulations and docking methods were used to predict the DNA binding affinity of ruthenium complexes and with good visualisation images supporting with experimental results.

The cell viability decreased with increasing concentrations of three complexes. The IC50 values are 21.7%, 22.4% and 23.1% for 1, 2 and 3 complexes towards HeLa cell lines respectively. Our data demonstrated that the Ru(II) polypyridyl complex binds to DNA and thereby induces apoptosis in tumor cells, suggesting that anti-tumor activity of the Ru(II) complex could be related to its interaction with DNA.Figure optionsDownload as PowerPoint slide