Linked Life Data

14729322

Source:http://linkedlifedata.com/resource/pubmed/id/14729322

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
2004-1-19
pubmed:abstractText
The coordination of the antimetastatic agent NAMI-A, [H(2)im][trans-RuCl(4)(dmso-S)(Him)], (Him=imidazole; dmso=dimethyl sulfoxide), to the DNA model base 9-methyladenine (9-MeAde) was investigated in water. NMR spectroscopy was first applied for the study of the molecular stability and hydrolysis of NAMI-A in aqueous solution over a range of pH (3.0-7.4) and chloride ion concentrations (0-1 M) at 37.0 degrees C. In physiological conditions (phosphate buffer, pH 7.4) NAMI-A disappears from the solution in 15 min due to chloride and dmso hydrolysis, leading to uncharacterised poly-oxo Ru species. Conversely, at lower pH (3.0-6.0) and in water (pH approximately 5.5), only a partial dmso hydrolysis occurs, slowly forming the [trans-RuCl(4)(H(2)O)(Him)](-) complex. This latter species coordinates to 9-MeAde (via the N7 of 9-MeAde), forming the [trans-RuCl(4)(9-MeAde)(Him)](-) complex. NAMI-A and [trans-RuCl(4)(H(2)O)(Him)](-) give comparable intracellular ruthenium concentrations and accumulate in KB cells (human mouth carcinoma) and accumulate these at the G(2)/M phase, while poly-oxo Ru species do not, and their cell uptake is reduced to 50%. On the contrary, G(2)/M arrest and protein content in the murine metastatic cell line metGM, are not influenced by NAMI-A hydrolysis. Hydrolysed NAMI-A species apparently are easier taken up by the metGM cells, showing intracellular ruthenium concentrations one order of magnitude greater than those of intact NAMI-A. Therefore, it is proposed that the selective antimetastatic activity of NAMI-A during in vivo experiments can be attributed to its hydrolysed species.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Feb
pubmed:issn
0162-0134
pubmed:author
pubmed:issnType
Print
pubmed:volume
98
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
402-12
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed:year
2004
pubmed:articleTitle
The hydrolysis of the anti-cancer ruthenium complex NAMI-A affects its DNA binding and antimetastatic activity: an NMR evaluation.
pubmed:affiliation
Leiden Institute of Chemistry, Gorlaeus Laboratories, Leiden University, P.O. Box 9502, 2300 RA Leiden, The Netherlands.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't