Effects of intercalative ligands on the DNA binding, DNA topoisomerase II and DNA transcription inhibition of polypyridyl ruthenium(II) complexes

To investigate the effect of intercalative ligand on their biological activity, five new complexes [Ru(bpy)2(dpq)](ClO4)2 (bpy = 2,2′-bipyridine, dpq = dipyridoquinoxaline), [Ru(bpy)2(dicnq)](ClO4)2 (dicnq = pyrazino[2,3-f]phenanthroline-2,3-dicarbonitrile), [Ru(bpy)2(dppp3)](ClO4)2 (dppp3 = pyrido[3′,4′:5,6]pyrazino[2,3-f][1,10]phenanthroline), [Ru(bpy)2(dppp2)](ClO4)2 (dppp2 = pyrido[2′,3′:5,6]pyrazino[2,3-f][1,10]phenanthroline) and [Ru(bpy)2(OCH3-dppz)](ClO4)2 (OCH3-dppz = 11-methoxy-dipyrido[3,2-a:2′,3′-c]phenazine) have been synthesized and characterized in detail by 1H NMR spectroscopy, mass spectrometry and elemental analysis. Their interaction with calf thymus DNA and the inhibitory activity towards topoisomerase II and T7 RNA polymerase have been examined by a series of experimental methods. The results suggest that a high DNA-binding affinity is important for their topoisomerase II and DNA transcription inhibition. Intercalative ligands with more extended aromatic area, better conjugate effect and presence of electron-withdrawing substituted groups are beneficial to the DNA intercalation and enzymatic inhibition of their polypyridyl Ru(II) complexes.

Five new Ru(II) complexes have been synthesized and characterized. Their interaction with calf thymus DNA and the inhibitory activity towards topoisomerase II and T7 RNA polymerase were investigated. The results suggest that the extended aromatic area, better conjugate effect and the existence of electron-withdrawing group on the intercalative ligand are beneficial to the DNA intercalation and enzymatic inhibition of their complexes.Figure optionsDownload as PowerPoint slideHighlights
► Five new polypyridyl Ru(II) complexes were synthesized and characterized.
► Their DNA-binding trend has been testified by experimental and theoretical methods.
► Their inhibitory activity towards topoisomerase and RNA polymerase has been studied.
► Relationship between their structures and activities has been concluded.