title: Cellular uptake, cytotoxicity, apoptosis, DNA-binding, photocleavage and molecular docking studies of ruthenium(II) polypyridyl complexes.
abstract: 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)× 10(5), 3.87 (± 0.04) × 10(5), 2.79 (±0.07) × 10(5) 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.
authors.affiliation: Department of Chemistry, Osmania University, Hyderabad 500007, India.
authors.forename: A
authors.initials: A
authors.lastname: Srishailam
authors.affiliation: Department of Chemistry, Osmania University, Hyderabad 500007, India.
authors.forename: Yata Praveen
authors.initials: YP
authors.lastname: Kumar
authors.affiliation: Department of Chemistry, Osmania University, Hyderabad 500007, India.
authors.forename: P
authors.initials: P
authors.lastname: Venkat Reddy
authors.affiliation: Department of Chemistry, Nizam College, Osmania University, Hyderabad 500001, India.
authors.forename: Navaneetha
authors.initials: N
authors.lastname: Nambigari
authors.affiliation: Department of Chemistry, Nizam College, Osmania University, Hyderabad 500001, India.
authors.forename: Uma
authors.initials: U
authors.lastname: Vuruputuri
authors.affiliation: Department of Biochemistry, Osmania University, Hyderabad 500007, India.
authors.forename: Surya S
authors.initials: SS
authors.lastname: Singh
authors.affiliation: Department of Chemistry, Osmania University, Hyderabad 500007, India. Electronic address: ssnsirasani@gmail.com.
authors.forename: S
authors.initials: S
authors.lastname: Satyanarayana
mesh_terms: D000890:Anti-Infective Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D001665:Binding Sites; D056831:Coordination Complexes / Q000737:chemistry / Q000378:metabolism / Q000633:toxicity*; D018360:Crystallography, X-Ray; D004247:DNA / Q000737:chemistry* / Q000378:metabolism; D053837:DNA Cleavage / Q000187:drug effects*; D004926:Escherichia coli / Q000187:drug effects; D006367:HeLa Cells; D006801:Humans; D007364:Intercalating Agents / Q000737:chemistry / Q000378:metabolism / Q000633:toxicity; D008826:Microbial Sensitivity Tests; D008968:Molecular Conformation; D056004:Molecular Dynamics Simulation; D009690:Nucleic Acid Conformation; D012428:Ruthenium / Q000737:chemistry*; D013211:Staphylococcus aureus / Q000187:drug effects; D014783:Viscosity
chemical_list: D000890:Anti-Infective Agents; D056831:Coordination Complexes; D007364:Intercalating Agents; D012428:Ruthenium; D004247:DNA
keywords: Anti-tumour activity; Apoptosis and flow cytometry; Binding affinity; Cell viability; Cytocoxicity