Linked Life Data

11640915

Source:http://linkedlifedata.com/resource/pubmed/id/11640915

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
2001-10-19
pubmed:abstractText
Absorption, melting temperature and linear dichroism measurements were performed to investigate the interaction with DNA of a series of 16 tricyclic and tetracyclic compounds related to the antiviral agent B-220. The relative DNA affinity of the test compounds containing an indolo[2,3-b]quinoxaline, pyridopyrazino[2,3-b]indoles or pyrazino[2,3-b]indole planar chromophore varies significantly depending on the nature of the side chain grafted onto the indole nitrogen. Compounds with a dimethylaminoethyl chain strongly bind to DNA and exhibit a preference for GC-rich DNA sequences, as revealed by DNase I footprinting. Weaker DNA interactions were detected with those bearing a morpholinoethyl side chain. The incorporation of a 2,3-dihydroxypropyl side chain does not reinforce the DNA interaction compared with the unsubstituted analogues. Both the DNA relaxation assay and cytotoxicity study using two human leukemia cell lines sensitive (HL-60) or resistant (HL-60/MX2) to the antitumor drug mitoxantrone, indicate that topoisomerase II is not a privileged target for the test compounds which only weakly interfere with the catalytic activity of the DNA cleaving enzyme. Cytometry studies showed that the most cytotoxic compounds induce a massive accumulation of cells in the G2/M phase of the cell cycle. Collectively, the data show a relationship between DNA binding and cytotoxicity in the indolo[2,3-b]quinoxaline series.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Oct
pubmed:issn
0009-2797
pubmed:author
pubmed:issnType
Print
pubmed:day
25
pubmed:volume
138
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
59-75
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed:year
2001
pubmed:articleTitle
DNA interaction and cytotoxicity of a new series of indolo[2,3-b]quinoxaline and pyridopyrazino[2,3-b]indole derivatives.
pubmed:affiliation
INSERM U-524 et Laboratoire de Pharmacologie Antitumorale du Centre Oscar Lambret, IRCL, Place de Verdun, 59045 Cedex, Lille, France.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't