Source:http://linkedlifedata.com/resource/pubmed/id/14971891
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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
5
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| pubmed:dateCreated |
2004-2-19
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| pubmed:abstractText |
Ruthenium compounds have gained large interest for their potential application as chemotherapeutic agents, and in particular the complexes of the type (X)[trans-RuCl4(dmso-S)L] (X = HL or Na, NAMI-A or NAMI, respectively, for L = imidazole) are under investigation for their antimetastatic properties. The NAMI(-A)-like compounds are prodrugs that hydrolyze in vivo, and the investigation of their hydrolytic properties is therefore important for determining the nature of the potential active species. The NAMI-A-type Ru(III) complex 1, (Hdmtp)[trans-RuCl4(dmso-S)(dmtp)] (dmtp is 5,7-dimethyl[1,2,4]triazolo[1,5-a]pyrimidine), and the corresponding sodium analogue 2, (Na)[trans-RuCl4(dmso-S)(dmtp)], were synthesized. The hydrolyses of 1 and 2 in water as well as in buffered solutions were studied, and the first hydrolysis product, [mer-RuCl3(H2O)(dmso-S)(dmtp)].H2O (3), was isolated and characterized. The molecular structures of 1 and 3 were determined by single-crystal X-ray diffraction analyses and prove the importance of the hydrogen-bonding properties of dmtp to stabilize hydrolysis products. In vitro 1 (a) is not cytotoxic on tumor cells, following challenges from 1 to 72 h and concentrations up to 100 microM, (b) inhibits matrigel invasion at 0.1 mM and MMP-9 activity with an IC50 of about 1 mM, and (c) is devoid of pronounced effects on cell distribution among cell cycle phases. In vivo compound 1, similar to NAMI-A, significantly inhibits metastasis growth in mice bearing advanced MCa mammary carcinoma tumors. In the lungs, 1 is significantly less concentrated than NAMI-A, whereas no differences between these two compounds were found in other organs such as tumor, liver, and kidney. However, 1 caused edema and necrotic areas on liver parenchyma that are more pronounced than those caused by NAMI-A. Conversely, glomerular and tubular changes on kidney are less extensive than with NAMI-A. In conclusion, 1 confirms the excellent antimetastatic properties of this class of NAMI-A-type compounds and qualifies as an interesting alternative to NAMI-A for treating human cancers.
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| pubmed:language |
eng
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| pubmed:journal | |
| pubmed:citationSubset |
IM
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| pubmed:chemical | |
| pubmed:status |
MEDLINE
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| pubmed:month |
Feb
|
| pubmed:issn |
0022-2623
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| pubmed:author | |
| pubmed:issnType |
Print
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| pubmed:day |
26
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| pubmed:volume |
47
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| pubmed:owner |
NLM
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| pubmed:authorsComplete |
Y
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| pubmed:pagination |
1110-21
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| pubmed:dateRevised |
2006-11-15
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| pubmed:meshHeading |
pubmed-meshheading:14971891-Animals,
pubmed-meshheading:14971891-Antineoplastic Agents,
pubmed-meshheading:14971891-Cell Cycle,
pubmed-meshheading:14971891-Cell Line, Tumor,
pubmed-meshheading:14971891-Cell Survival,
pubmed-meshheading:14971891-Crystallography, X-Ray,
pubmed-meshheading:14971891-Drug Screening Assays, Antitumor,
pubmed-meshheading:14971891-Hydrolysis,
pubmed-meshheading:14971891-Kidney,
pubmed-meshheading:14971891-Liver,
pubmed-meshheading:14971891-Lung Neoplasms,
pubmed-meshheading:14971891-Magnetic Resonance Spectroscopy,
pubmed-meshheading:14971891-Mammary Neoplasms, Animal,
pubmed-meshheading:14971891-Matrix Metalloproteinase 9,
pubmed-meshheading:14971891-Mice,
pubmed-meshheading:14971891-Molecular Structure,
pubmed-meshheading:14971891-Neoplasm Invasiveness,
pubmed-meshheading:14971891-Neoplasm Metastasis,
pubmed-meshheading:14971891-Organometallic Compounds,
pubmed-meshheading:14971891-Ruthenium,
pubmed-meshheading:14971891-Spectrophotometry, Ultraviolet,
pubmed-meshheading:14971891-Structure-Activity Relationship,
pubmed-meshheading:14971891-Tissue Distribution
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| pubmed:year |
2004
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| pubmed:articleTitle |
Synthesis and chemical-pharmacological characterization of the antimetastatic NAMI-A-type Ru(III) complexes (Hdmtp)[trans-RuCl4(dmso-S)(dmtp)], (Na)[trans-RuCl4(dmso-S)(dmtp)], and [mer-RuCl3(H2O)(dmso-S)(dmtp)] (dmtp = 5,7-dimethyl[1,2,4]triazolo[1,5-a]pyrimidine).
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| pubmed:affiliation |
Leiden Institute of Chemistry, Gorlaeus Laboratories, Leiden University, P.O. Box 9502, 2300 RA Leiden, The Netherlands. a.velders@chem.leidenuniv.nl
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| pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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