Linked Life Data

11585450

Source:http://linkedlifedata.com/resource/pubmed/id/11585450

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
21
pubmed:dateCreated
2001-10-4
pubmed:abstractText
Dimeric DNA cross-linking compounds have emerged as important new antitumor agents. We report the synthesis and biochemical evaluation of a select set of dimeric mitomycins in which the two mitomycin units are tethered at either the mitomycin C(7) amino or the aziridine N(1a) positions. Significantly, mitomycin C (1) itself is the prototypical bioreductive DNA cross-linking agent. DNA cross-linking experiments using a denaturing-gel-electrophoresis-based assay showed that the extent of DNA cross-linking for select dimeric mitomycins can exceed that of the parent compound, mitomycin C, and that the reaction proceeds, in part, at the two distal C(1) sites in the mitomycins. The efficiency of DNA cross-linking depended on the nature of the linker and the position of linker unit's attachment. When we compared the efficiency of DNA cross-linking for the dimeric mitomycins with their in vitro cytotoxicities in cultured human tumor cells, we observed a poor correlation. The mitomycins that gave the highest levels of DNA cross-linked adducts displayed the weakest cytotoxicities. These findings determined that the denaturing-gel-electrophoresis-based assay was a poor predictor of cytotoxic activity.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Oct
pubmed:issn
0022-2623
pubmed:author
pubmed:issnType
Print
pubmed:day
11
pubmed:volume
44
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
3453-62
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed:year
2001
pubmed:articleTitle
Synthesis, DNA cross-linking activity, and cytotoxicity of dimeric mitomycins.
pubmed:affiliation
Department of Chemistry, University of Houston, Houston, Texas 77204-5641, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S.