Linked Life Data

14559834

Source:http://linkedlifedata.com/resource/pubmed/id/14559834

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
19
pubmed:dateCreated
2003-10-15
pubmed:abstractText
The present study describes the biological in vitro and in vivo evaluation of 2-methoxy derivatives of estrogenic inhibitors of steroid sulfatase, namely 3-sulfamoyloxy-17alpha-p-tert-butylbenzyl(or benzyl)-1,3,5 (10)-estratrien-17beta-ols. The addition of the 2-methoxy group conserves the potent inhibitory effect on steroid sulfatase activity (IC(50)s of 0.024 and 0.040 nM) while removing the estrogenic action. Using an ovariectomized mouse model, we show that the first generation of steroid sulfatase inhibitors tested, 3-sulfamoyloxy-17alpha-p-tert-butylbenzyl(or benzyl)estra-1,3,5 (10)-trien-17beta-ols and estrone-3-O-sulfamate, are estrogenic compounds stimulating estrogen-sensitive uterine growth. Interestingly, the 2-methoxy-3-sulfamoyloxy-17alpha-benzylestra-1,3,5 (10)-trien-17beta-ol (7) has no estrogenic activity but efficiently blocks (s.c. and p.o.) uterine growth induced by estrone sulfate, which is converted into estrone and then estradiol by steroid sulfatase and type 1 17beta-hydroxysteroid dehydrogenase, respectively. This report clearly shows that a steroid sulfatase inhibitor can efficiently block estrogen action from the inactive precursor estrone sulfate, in vitro and in vivo.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Oct
pubmed:issn
0008-5472
pubmed:author
pubmed:issnType
Print
pubmed:day
1
pubmed:volume
63
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
6442-6
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed:year
2003
pubmed:articleTitle
Inhibition of estrone sulfate-induced uterine growth by potent nonestrogenic steroidal inhibitors of steroid sulfatase.
pubmed:affiliation
Medicinal Chemistry Division, Oncology and Molecular Endocrinology Research Center, Centre Hospitalier Universitaire de Québec-Pavillon CHUL, 2705 Laurier Boulevard, Québec, Canada G1V 4G2.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't