In vitro and in vivo biological activity screening of Ru(III) complexes involving 6-benzylaminopurine derivatives with higher pro-apoptotic activity than NAMI-A
Language English Country United States Media print-electronic
Document type Journal Article, Research Support, Non-U.S. Gov't
PubMed
21536006
DOI
10.1016/j.jinorgbio.2011.04.002
PII: S0162-0134(11)00082-1
Knihovny.cz E-resources
- MeSH
- Apoptosis drug effects MeSH
- Benzyl Compounds MeSH
- Dimethyl Sulfoxide analogs & derivatives pharmacology MeSH
- Kinetin chemical synthesis chemistry pharmacology MeSH
- Coordination Complexes chemical synthesis chemistry pharmacology MeSH
- Crystallography, X-Ray MeSH
- Leukemia L1210 drug therapy pathology MeSH
- Humans MeSH
- Mitosis drug effects MeSH
- Molecular Conformation MeSH
- Mice, Inbred DBA MeSH
- Mice MeSH
- Cell Line, Tumor MeSH
- Necrosis MeSH
- Organometallic Compounds pharmacology MeSH
- Antineoplastic Agents chemical synthesis chemistry pharmacology MeSH
- Purines MeSH
- Ruthenium * MeSH
- Drug Screening Assays, Antitumor MeSH
- Ruthenium Compounds MeSH
- Neoplasm Transplantation MeSH
- Animals MeSH
- Check Tag
- Humans MeSH
- Mice MeSH
- Female MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Names of Substances
- benzylaminopurine MeSH Browser
- Benzyl Compounds MeSH
- Dimethyl Sulfoxide MeSH
- imidazolium-bis(imidazole)dimethylsulfoxideimidazotetrachlororuthenate(III) MeSH Browser
- Kinetin MeSH
- Coordination Complexes MeSH
- Organometallic Compounds MeSH
- Antineoplastic Agents MeSH
- Purines MeSH
- Ruthenium * MeSH
- Ruthenium Compounds MeSH
A series of novel octahedral ruthenium(III) complexes involving 6-benzylaminopurine (L) derivatives as N-donor ligands has been prepared by the reaction of [(DMSO)(2)H][trans-RuCl(4)(DMSO)(2)] with the corresponding L derivative. The complexes 1-12 have the general compositions trans-[RuCl(4)(DMSO)(n-Cl-LH)]⋅xSol (1-3), trans-[RuCl(4)(DMSO)(n-Br-LH)]·xSol (4-6), trans-[RuCl(4)(DMSO)(n-OMe-LH)]·xSol (7-9) and trans-[RuCl(4)(DMSO)(n-OH-LH)]·xSol (10-12); n=2, 3, and 4, x=0-1.5; and Sol = H(2)O, DMSO, EtOH and/or (Me)(2)CO. The complexes have been thoroughly characterized by elemental analysis, UV-visible, FTIR, Raman, and EPR spectroscopy, ES+(positive ionization electrospray) mass spectrometry, thermal analysis, cyclic voltammetry, magnetic and conductivity measurements. The X-ray molecular structure of trans-[RuCl(4)(DMSO)(3-Br-LH)]⋅(Me)(2)CO (5) revealed the distorted octahedral coordination in the vicinity of the central atom, and also confirmed that the 3-Br-L ligand is present as the N3-protonated N7-H tautomer and is coordinated to Ru(III) through the N9 atom of the purine moiety. The tested complexes have been found to be in vitro non-cytotoxic against K562, G361, HOS and MCF7 human cancer cell lines with IC(50)>100μM in contrast to the moderate results regarding the antiradical activity with IC(50)≈10(-3)M. On the contrary, in vivo antitumor activity screening showed that the prepared Ru(III) complexes possess higher pro-apoptotic activity than NAMI-A. The reduction of Ru(III) to Ru(II) and Ru(II)-species formation in tumor tissues was confirmed by means of a simple method of detection and visualization of intracellular Ru(II) by fluorescence microscopy. The originality of this method is based on the preparation of a Ru(II)-bipyridine complex in situ.
References provided by Crossref.org
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