Linked Life Data

10514278

Source:http://linkedlifedata.com/resource/pubmed/id/10514278

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
20
pubmed:dateCreated
1999-11-4
pubmed:abstractText
As part of our continuing search for potential anticancer drug candidates in the 2-aryl-1,8-naphthyridin-4-one series, we have synthesized a series of substituted 2-thienyl-1, 8-naphthyridin-4-ones. Most compounds showed significant cytotoxic effects (log GI(50) < -4.0; log molar drug concentration required to cause 50% growth inhibition) against a variety of human tumor cell lines in the National Cancer Institute's in vitro screen, including cells derived from solid tumors such as non-small-cell lung, colon, central nervous system, melanoma, ovarian, prostate, and breast cancers. The most active compounds (31-33,40) demonstrated strong cytotoxic effects with ED(50) values in the micromolar or submicromolar range in most of the tumor cell lines. The most cytotoxic compounds inhibited tubulin polymerization at concentrations substoichiometric to the tubulin concentration. The most potent inhibitors of polymerization (40,42,43) had effects comparable to those of the potent antimitotic natural products podophyllotoxin and combretastatin A-4 and to that of NSC 664171, a particularly potent, structurally related analogue. Only compound 40 was a potent inhibitor of the binding of radiolabeled colchicine to tubulin, and it was both the most cytotoxic agent and the most effective inhibitor of polymerization among the newly synthesized compounds.
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
7
pubmed:volume
42
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
4081-7
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed:year
1999
pubmed:articleTitle
Antitumor agents. 196. Substituted 2-thienyl-1,8-naphthyridin-4-ones: their synthesis, cytotoxicity, and inhibition of tubulin polymerization.
pubmed:affiliation
Natural Products Laboratory, Division of Medicinal Chemistry, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S.