Linked Life Data

2626034

Source:http://linkedlifedata.com/resource/pubmed/id/2626034

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1-6
pubmed:dateCreated
1990-3-30
pubmed:abstractText
The biological activities of tamoxifen derivatives that contain various side chain alterations were studied using a T47D breast cancer cell growth assay in vitro. We studied the activity of various analogs to determine the important aspects of side chain composition and aryl ring positioning on antiestrogenic activity. Previous studies utilizing a rat pituitary cell prolactin synthesis assay have shown that substitution of the aminoethoxy side chain for an allyl side chain resulted in agonist activity, whereas the addition of a glyceryl side chain produced antiestrogenic activity. In the present study utilizing T47D cells, compounds with alkyl or allyl substitutions were partial agonists, as were compounds with bulky para-substituted benzyl group constituents. A tamoxifen derivative with a side chain containing an ethyl ester was antiestrogenic (IC50 = 2 x 10(-6) M) and effectively inhibited estradiol (10(-10) M) stimulation of growth. However, a compound with a short similar methyl ester-containing side chain did not possess any activity. Compounds with carbinol-containing side chains were antiestrogenic (IC50 = 2.8-3.5 x 10(-7) M). All of the compounds displaying antiestrogenic activity could be "rescued" by incubation with estradiol (10(-8) M) and therefore were not nonspecifically toxic to the cells. These results support the hypothesis that the presence of a lone pair of electrons within the side chain region of tamoxifen may be required for antiestrogenic activity. Also, nonplanar placement of the aryl ring of the triphenylethylene-type of compound is critical for potency.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:issn
0022-4731
pubmed:author
pubmed:issnType
Print
pubmed:volume
34
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
407-11
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed:year
1989
pubmed:articleTitle
Structural components necessary for the antiestrogenic activity of tamoxifen.
pubmed:affiliation
Department of Human Oncology, University of Wisconsin Clinical Cancer Center, Madison 53792.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S.