Linked Life Data

14761199

Source:http://linkedlifedata.com/resource/pubmed/id/14761199

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
4
pubmed:dateCreated
2004-2-5
pubmed:abstractText
Aminoalkyl-substituted monomeric and dimeric dihydrodipyridopyrazines have been synthesized and evaluated as antitumor agents. Potent cytotoxic compounds were identified in both series. Biochemical and biophysical studies indicated that all these compounds strongly stabilized the duplex structure of DNA and some of them elicited a selectivity for GC-rich sequences. Sequence recognition by of the dimeric dihydrodipyridopyrazines is reminiscent of that of certain antitumor bisnaphthalimides. Compared to monomers, corresponding dimeric derivatives showed higher affinity for DNA. This property was attributed to a bisintercalative binding to DNA. This assumption was indirectly probed by electric linear dichroism and DNA relaxation experiments. DNA provides a bioreceptor for these dihydrodipyridopyrazine derivatives, but no poisoning of human topoisomerases I or II was detected. Most of the compounds efficiently inhibited the growth of L1210 murine leukemia cells and perturbed the cell cycle progression (with a G2/M block in most cases). A weak but noticeable in vivo antitumor activity was observed with one of the dimeric compounds. This studies identifies monomeric and dimeric dihydrodipyridopyrazines as a new class of DNA-targeted antitumor agents.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Feb
pubmed:issn
0022-2623
pubmed:author
pubmed:issnType
Print
pubmed:day
12
pubmed:volume
47
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
978-87
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed:year
2004
pubmed:articleTitle
Synthesis of mono- and bisdihydrodipyridopyrazines and assessment of their DNA binding and cytotoxic properties.
pubmed:affiliation
Institut de Chimie Organique et Analytique UMR-CNRS 6005, UFR de Sciences, Université d'Orléans, rue de Chartres, BP 6759, 45067 Orléans Cedex 2, France.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't