title: 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).
abstract: 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.
authors: Key Lab of Environment-friendly Chemistry and Application in Ministry of Education, Xiangtan University, Xiangtan 411105, China.
authors: Xiaojun
authors: X
authors: He
authors: Key Lab of Environment-friendly Chemistry and Application in Ministry of Education, Xiangtan University, Xiangtan 411105, China.
authors: Lianhe
authors: L
authors: Jin
authors: College of Chemistry, Xiangtan University, Xiangtan 411105, China. Electronic address: lfwyxh@yeah.net.
authors: Lifeng
authors: L
authors: Tan
mesh_terms: D000818:Animals; D001665:Binding Sites; D001667:Binding, Competitive / Q000187:drug effects; D002417:Cattle; D016923:Cell Death / Q000187:drug effects; D056831:Coordination Complexes / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D004247:DNA / Q000378:metabolism*; D004264:DNA Topoisomerases, Type I / Q000378:metabolism*; D004250:DNA Topoisomerases, Type II / Q000378:metabolism*; D004583:Electrons; D004587:Electrophoresis, Agar Gel; D006367:HeLa Cells; D056945:Hep G2 Cells; D006801:Humans; D020128:Inhibitory Concentration 50; D007700:Kinetics; D011725:Pyridines / Q000494:pharmacology*; D012428:Ruthenium / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D012997:Solvents / Q000737:chemistry; D013050:Spectrometry, Fluorescence; D013056:Spectrophotometry, Ultraviolet; D013696:Temperature; D059003:Topoisomerase Inhibitors / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D014783:Viscosity / Q000187:drug effects
chemical_list: D056831:Coordination Complexes; D011725:Pyridines; D012997:Solvents; D059003:Topoisomerase Inhibitors; D012428:Ruthenium; D004247:DNA; C427203:calf thymus DNA; D004264:DNA Topoisomerases, Type I; D004250:DNA Topoisomerases, Type II; C023666:pyridine
keywords: Binding properties; Cytotoxicity; Dual inhibitors of topoisomerases; Ru(II) polypyridyl complexes