Linked Life Data

1658605

Source:http://linkedlifedata.com/resource/pubmed/id/1658605

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
5
pubmed:dateCreated
1991-12-19
pubmed:abstractText
With the aim of obtaining new inhibitors of topoisomerases, we have evaluated various heterocyclic quinone derivatives for their ability to induce topoisomerase I (Topo I)- or Topo II-associated DNA breaks, using P388 cell nuclear extract. Several compounds belonging to the indolo[3,2-c]quinoline-1,4-dione series have been shown to possess DNA-cleavage activity. Further analysis using purified Topo I and II preparations has indicated that the members of the series stimulate cleavable complex formation of both Topo I and II. 3-Methoxy-11H-pyrido[3',4':4,5]pyrrolo[3,2-c] quinoline-1,4-dione (AzalQD), one of the most active members of the series, stimulates cleavable complex formation and inhibits the catalytic activities of both eukaryotic Topo I and II, with, however, less potency than camptothecin and etoposide. Topo I cleavage site patterns for AzalQD and camptothecin were found to be nearly identical, with, however, some differences in cleavage site intensities. Use of filter binding assays also indicates that AzalQD is at least 10 times more potent against Topo I than against Topo II. Structure-activity relationships of indoloquinolinedione derivatives have been established and have shown that Topo I and II inhibitions are strongly linked, with a dose-selective preference towards Topo I. AzalQD does not display detectable DNA-unwinding properties. AzalQD induces a preferential cytotoxicity for the yeast strain JN2-134 bearing the human top1 gene under the control fo the GAL1 promoter, indicating that Topo I inhibition is responsible for the yeast cytotoxicity. These data indicate that AzalQD and its structural analogs represent a new distinct class of eukaryotic Topo I and II inhibitors.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Nov
pubmed:issn
0026-895X
pubmed:author
pubmed:issnType
Print
pubmed:volume
40
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
699-706
pubmed:dateRevised
2010-11-18
pubmed:meshHeading
pubmed:year
1991
pubmed:articleTitle
Inhibition of eukaryotic DNA topoisomerase I and II activities by indoloquinolinedione derivatives.
pubmed:affiliation
Rhône Poulenc Rorer, Centre de Recherche de Vitry-Alfortville, Vitry sur Seine, France.
pubmed:publicationType
Journal Article