Studies on the DNA binding and anticancer activity of Ru(ii) polypyridyl complexes by using a (2-(4-(diethoxymethyl)-1H-imidazo[4,5-f][1,10] phenanthroline)) intercalative ligand

Abstract

A new ligand, depip (2-(4-(diethoxymethyl)-1H-imidazo[4,5-f][1,10] phenanthroline)), and its three mononuclear Ru(II)polypyridyl complexes, [Ru(phen)₂(depip)](ClO₄)₂·2H₂O (1), [Ru(bpy)₂(depip)](ClO₄)₂·2H₂O (2), and [Ru(dmb)₂(depip)](ClO₄)₂·2H₂O (3) have been synthesized and characterized by elemental analysis, FT-IR, ¹H-NMR, ¹³C-NMR, UV-vis and mass spectrometry. The interaction of all three Ru(II) complexes with CT DNA was investigated using optical spectroscopy and viscosity measurements. The results indicate that all three complexes bind to DNA through an intercalative mode, albeit with different binding constants. Molecular docking simulation studies indicate the involvement of hydrogen bonding and van der Waals interactions in the binding and the Gold scores are in tune with the experimentally measured binding constants. Interestingly, all three complexes show significant DNA cleaving activity. All three Ru(II) polypyridyl complexes were examined for their antimicrobial and anticancer activities. Antimicrobial activity was assessed against Escherichia coli, Staphylococcus aureus and Bacillus subtilis. The anticancer activities of these three complexes were examined on the cervical cancer HeLa cell line. The MTT assay shows the anti-proliferative activity of the complexes and they show a limited cytotoxic effect on the normal human embryonic kidney cell line (HEK 293). Cell cycle analysis shows that all these complexes perturb cell cycle dynamics and finally causing cell death by the induction of apoptosis.