Synthesis, DNA-binding and topoisomerase inhibitory activity of ruthenium(II) polypyridyl complexes

Two ruthenium(II) complexes [Ru(bpy)2(bfipH)]2+ (1) and [Ru(phen)2(bfipH)]2+ (2) have been synthesized and characterized. The DNA-binding behaviors of complexes were studied by using spectroscopic and viscosity measurements. Results suggested that the two complexes bind to DNA in an intercalative mode. Complexes 1 and 2 can efficiently photocleave pBR322 DNA in vitro under irradiation, singlet oxygen (1O2) was proved to contribute to the DNA photocleavage process. Topoisomerase inhibition and DNA strand passage assay confirmed that two Ru(II) complexes acted as efficient dual inhibitors of topoisomerases I and II. In MTT cytotoxicity studies, two Ru(II) complexes exhibited antitumor activity against BEL-7402, HeLa, MCF-7 tumor cells. The AO/EB staining assay indicated that Ru(II) complexes could induce the apoptosis of HeLa cells.

Graphical abstractTwo ruthenium complexes [Ru(bpy)2(bfipH)]2+ (1) and [Ru(phen)2(bfipH)]2+ (2) were found to act as efficient dual inhibitors of topoisomerases I and II. Figure optionsDownload full-size imageDownload as PowerPoint slideResearch highlights► Two novel DNA-intercalating ruthenium(II) complexes [Ru(bpy)2(bfipH)]2+ (1) and [Ru(phen)2(bfipH)]2+ (2) were confirmed to act as efficient dual inhibitors of topoisomerases I and II. ► Both complexes exhibited antitumor activity against BEL-7402, HeLa, MCF-7 tumor cells. ► The AO/EB staining assay testified that Ru(II) complexes induce the apoptosis of HeLa cells.