Linked Life Data

16679562

Source:http://linkedlifedata.com/resource/pubmed/id/16679562

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
2006-5-8
pubmed:abstractText
The new imidazole-coordinated chemotherapeutics with low epithelial toxicity (NICE) presented in this article feature innovative drugs that combine epithelial toxicity comparable with that of carboplatin with novel carrier ligands optimized for DNA interaction. Recent identification of the pivotal role of basolateral organic cation transporters (OCTs) in cisplatin nephrotoxicity by a new model system (electrical resistance breakdown assay) facilitated the search for substances with a favorable organotoxic profile. The assay uses the high transepithelial electrical resistance (TEER) of the C7-clone of Madin-Darby canine kidney (MDCK) cells and the exclusive basolateral expression of OCT2 in these cells. TEER and caspase-3 activity of MDCK-C7-cells grown on microfilter membranes were monitored in response to exposure of either the apical or basolateral plasma membrane to platinum complexes. The impact of complexes on cancer cell lines was evaluated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide tests. Effects of substituents on pharmacological properties of NICE were systematically investigated by introducing sterically demanding groups as well as electron-donating and electron-withdrawing groups. Derivatives of NICE showed different renal epithelial toxic profiles and effects on cancer cells. NICE were significantly less toxic than cis- or oxaliplatin. The chlorine substituted NICE had no effect on epithelial integrity but markedly cytotoxic activity against amelanotic melanoma cells. Together, side effect targeted screening for new anticancer drugs with the electrical resistance breakdown assay offers an interesting approach for identifying and investigating new compounds. NICE feature the first group of platinum-based cytostatics discovered by using this system for systematic screening of new chemotherapeutics with low renal epithelial toxicity.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:issn
1085-9195
pubmed:author
pubmed:issnType
Print
pubmed:volume
45
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
31-41
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed-meshheading:16679562-Animals, pubmed-meshheading:16679562-Antineoplastic Agents, pubmed-meshheading:16679562-Carboplatin, pubmed-meshheading:16679562-Caspase 3, pubmed-meshheading:16679562-Caspases, pubmed-meshheading:16679562-Cell Culture Techniques, pubmed-meshheading:16679562-Cell Line, pubmed-meshheading:16679562-Cell Line, Tumor, pubmed-meshheading:16679562-Cell Membrane, pubmed-meshheading:16679562-Cell Polarity, pubmed-meshheading:16679562-Cells, Cultured, pubmed-meshheading:16679562-Clone Cells, pubmed-meshheading:16679562-Dogs, pubmed-meshheading:16679562-Electric Impedance, pubmed-meshheading:16679562-Epithelial Cells, pubmed-meshheading:16679562-Imidazoles, pubmed-meshheading:16679562-Intracellular Membranes, pubmed-meshheading:16679562-Ligands, pubmed-meshheading:16679562-Molecular Conformation, pubmed-meshheading:16679562-Organic Cation Transport Proteins, pubmed-meshheading:16679562-Organoplatinum Compounds
pubmed:year
2006
pubmed:articleTitle
New imidazole-coordinated chemotherapeutics with low epithelial toxicity.
pubmed:affiliation
Institute of Physiology II, University of Münster, Germany. thomas.ludwig@yale.edu
pubmed:publicationType
Journal Article, Comparative Study