Linked Life Data

2909736

Source:http://linkedlifedata.com/resource/pubmed/id/2909736

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
1989-2-6
pubmed:abstractText
The nitroacridine derivative 9-[[3-(dimethylamino)propyl]amino]-1-nitroacridine (nitracrine) is selectively cytotoxic to hypoxic tumor cells in culture. However, the compound undergoes reductive metabolism too rapidly, with the reduction not being sufficiently inhibited by molecular oxygen in aerobic tissues, for it to demonstrate the same activity in vivo. In a search for derivatives with lower reduction potentials, we have synthesized and evaluated a series of derivatives bearing 4-substituents with a wide range of electronic properties. The one-electron reduction potentials (E(1] of these compounds, when compared under conditions of equivalent ionization, were highly correlated with sigma p values. However, at pH 7 the influence of substituent electronic properties was modified by prototrophic equilibria, with the basic nature of the acridine limiting the extent to which ring substituent electronic effects can be used to modulate reduction potential of the 1-nitro group. Nevertheless, comparison of the kinetics of the killing of AA8 cells under hypoxia suggests that some metabolic stabilization of the compounds can be achieved by the use of electron-donating substituents, with such compounds retaining the hypoxia-selective toxicity of nitracrine in cell culture. However, the 4-substituted nitracrines show no clear relationship between E(1) and cytotoxic potency, in distinct contrast to simpler nitroheterocycles such as nitroimidazoles.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jan
pubmed:issn
0022-2623
pubmed:author
pubmed:issnType
Print
pubmed:volume
32
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
23-30
pubmed:dateRevised
2008-11-21
pubmed:meshHeading
pubmed:year
1989
pubmed:articleTitle
Hypoxia-selective antitumor agents. 1. Relationships between structure, redox properties and hypoxia-selective cytotoxicity for 4-substituted derivatives of nitracrine.
pubmed:affiliation
Department of Pathology, University of Auckland School of Medicine, New Zealand.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't