Cellular uptake, cytotoxicity, apoptosis, DNA-binding, photocleavage and molecular docking studies of ruthenium(II) polypyridyl complexes
Autor: | P. Venkat Reddy, A. Srishailam, Yata Praveen Kumar, Uma Vuruputuri, Navaneetha Nambigari, Sirasani Satyanarayana, Surya S. Singh |
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Rok vydání: | 2014 |
Předmět: |
Staphylococcus aureus
Stereochemistry Phenanthroline Intercalation (chemistry) Molecular Conformation Biophysics chemistry.chemical_element Apoptosis Microbial Sensitivity Tests Molecular Dynamics Simulation Crystallography X-Ray Ruthenium HeLa Bipyridine chemistry.chemical_compound Anti-Infective Agents Coordination Complexes Escherichia coli Humans Radiology Nuclear Medicine and imaging DNA Cleavage Binding site Binding Sites Radiation Radiological and Ultrasound Technology biology Viscosity DNA biology.organism_classification Intercalating Agents chemistry Docking (molecular) Nucleic Acid Conformation HeLa Cells |
Zdroj: | Journal of Photochemistry and Photobiology B: Biology. 132:111-123 |
ISSN: | 1011-1344 |
Popis: | 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. |
Databáze: | OpenAIRE |
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