Linked Life Data

7083196

Source:http://linkedlifedata.com/resource/pubmed/id/7083196

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
8 Suppl
pubmed:dateCreated
1982-8-26
pubmed:abstractText
Various C19-steroidal derivatives have been synthesized and evaluated in biochemical assays for their ability to inhibit the biosynthesis of estrogens. Steroids with substitutions on the A or B ring were prepared by Michael addition of various thiol reagents to appropriate dienone intermediates. An in vitro assay using human placental microsomes was used to evaluate aromatase-inhibitory properties. Synthesized compounds that exhibited high inhibitory activity were further evaluated under initial velocity conditions to determine apparent Ki values. Several 7 alpha-substituted androstenediones were effective competitive inhibitors and have apparent Ki values ranging from 18 to 69 nM, with the apparent Km for androstenedione being 63 nM. The most effective competitive inhibitor tested is 7 alpha-(4'-amino)phenylthioandrost-4-ene-3,17-dione with an apparent Ki of 18 nM. Derivatives of this 7 alpha-thioether compound that contain alkylating moieties have been prepared as potential irreversible enzyme inhibitors and demonstrate varying abilities to inactivate the aromatase enzyme. The results of these studies demonstrate that large chemical functionalities such as an aromatic ring with polar substituents can be accommodated in or near the active site of aromatase and, in some cases, can enhance the affinity of the enzyme for the inhibitors.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Aug
pubmed:issn
0008-5472
pubmed:author
pubmed:issnType
Print
pubmed:volume
42
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
3334s-3337s
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed:year
1982
pubmed:articleTitle
Substituted C19 steroid analogs as inhibitors of aromatase.
pubmed:publicationType
Journal Article, Comparative Study, Research Support, U.S. Gov't, P.H.S.