Linked Life Data

3346911

Source:http://linkedlifedata.com/resource/pubmed/id/3346911

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
3
pubmed:dateCreated
1988-4-21
pubmed:abstractText
Antitumor activity against the Lewis lung carcinoma in mice is reported for the series of 36 acridine-substituted derivatives of the antileukemia agent amsacrine. This series is the one from which the analogue N,5-dimethyl-9-[(2-methoxysulfonylamino)phenylamino]-4-acridinecarboxamide (CI-921), presently in clinical trial, was chosen. The analogues also were tested in vitro by comparing growth inhibition data [IC50 values (concentration required to reduce growth of cultured cells to 50% of that of untreated cultures)], using L1210 murine leukemia cells and HCT-8 human colon carcinoma cells. Determined IC50 values were highly dependent on the culture medium used, and it was found that the presence of ascorbate in the medium had a major effect on the stability of compounds to oxidation. A survey of 115 analogues of amsacrine indicates that a low ratio of IC50 values (HCT-8/L1210) is necessary but not sufficient for good antitumor activity against the solid tumor. DNA binding constants did not in themselves predict activity, although they were related to dose potency. Other factors, such as drug lipophilicity, acridine base strength, and drug solubility, also are involved, probably in providing effective drug distribution. It is concluded that in vitro assay data provide information useful for drug design but that other factors also are important for in vivo activity.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Apr
pubmed:issn
0027-8874
pubmed:author
pubmed:issnType
Print
pubmed:day
6
pubmed:volume
80
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
195-9
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed:year
1988
pubmed:articleTitle
Derivatives of amsacrine: determinants required for high activity against Lewis lung carcinoma.
pubmed:affiliation
Cancer Research Laboratory, University of Auckland Medical School, New Zealand.
pubmed:publicationType
Journal Article, Comparative Study, Research Support, Non-U.S. Gov't