Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
1982-4-20
pubmed:abstractText
Forty-five 4,6-diamino-1,2-dihydro-2,2-dimethyl-1-(3-X-phenyl)-s-triazine inhibitors of dihydrofolate reductase (DHFR) and methotrexate (MTX) were tested on L5178Y/R murine tumor cell culture. The concentration of inhibitor causing a 50% decrease in growth rate was determined, and from these results a quantitative structure-activity relationship (QSAR) was developed. This QSAR is compared with QSAR for the same inhibitors acting on isolated DHFR and on L5178Y cell culture sensitive to MTX. The results show that very potent triazine inhibitors of resistant tumor cell growth can easily be made by making the triazines strongly hydrophobic. The optimum pi value for inhibition of MTX-sensitive cell culture is 0.8, while pi 0 for the resistant cell culture is about 6.0. The QSAR for MTX-sensitive and -resistant tumor cell culture inhibition is compared with the corresponding QSAR for Lactobacillus casei cells. Both the mammalian and bacterial cells appear to protect themselves from the highly hydrophilic MTX by erecting lipophilic barriers.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Feb
pubmed:issn
0022-2623
pubmed:author
pubmed:issnType
Print
pubmed:volume
25
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
157-61
pubmed:dateRevised
2008-11-21
pubmed:meshHeading
pubmed:year
1982
pubmed:articleTitle
A comparison of the inhibition of growth of methotrexate-resistant and -sensitive leukemia cells in culture by triazines. Evidence for a new mechanism of cell resistance to methotrexate.
pubmed:publicationType
Journal Article, Comparative Study, Research Support, U.S. Gov't, P.H.S.