Luminescent ruthenium complexes for theranostic applications
| Autor: | Nicholas Farrell, Juliana Cheleski, Erica J. Peterson, Carolina R. Cardoso, Rose M. Carlos, Márcia V. S. Lima, Tiago Venâncio |
|---|---|
| Rok vydání: | 2014 |
| Předmět: |
Circular dichroism
Stereochemistry Serum albumin chemistry.chemical_element Antineoplastic Agents Apoptosis Ruthenium chemistry.chemical_compound Structure-Activity Relationship 2 2'-Dipyridyl Coordination Complexes Cell Line Tumor Drug Discovery medicine Imidazole Non-covalent interactions Humans Luminescent Agents Serum Albumin Cell Proliferation chemistry.chemical_classification biology Caspase 3 Imidazoles Isothermal titration calorimetry Cell Cycle Checkpoints Human serum albumin Crystallography chemistry biology.protein Molecular Medicine Drug Screening Assays Antitumor Poly(ADP-ribose) Polymerases Tumor Suppressor Protein p53 medicine.drug Histamine Phenanthrolines Protein Binding |
| Zdroj: | Journal of medicinal chemistry. 57(11) |
| ISSN: | 1520-4804 |
| Popis: | The water-soluble and visible luminescent complexes cis-[Ru(L-L)2(L)2](2+) where L-L = 2,2-bipyridine and 1,10-phenanthroline and L= imidazole, 1-methylimidazole, and histamine have been synthesized and characterized by spectroscopic techniques. Spectroscopic (circular dichroism, saturation transfer difference NMR, and diffusion ordered spectroscopy NMR) and isothermal titration calorimetry studies indicate binding of cis-[Ru(phen)2(ImH)2](2+) and human serum albumin occurs via noncovalent interactions with K(b) = 9.8 × 10(4) mol(-1) L, ΔH = -11.5 ± 0.1 kcal mol(-1), and TΔS = -4.46 ± 0.3 kcal mol(-1). High uptake of the complex into HCT116 cells was detected by luminescent confocal microscopy. Cytotoxicity of cis-[Ru(phen)2(ImH)2](2+) against proliferation of HCT116p53(+/+) and HCT116p53(-/-) shows IC50 values of 0.1 and 0.7 μmol L(-1). Flow cytometry and western blot indicate RuphenImH mediates cell cycle arrest in the G1 phase in both cells and is more prominent in p53(+/+). The complex activates proapoptotic PARP in p53(-/-), but not in p53(+/+). A cytostatic mechanism based on quantification of the number of cells during the time period of incubation is suggested. |
| Databáze: | OpenAIRE |
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