Linked Life Data

16078844

Source:http://linkedlifedata.com/resource/pubmed/id/16078844

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
16
pubmed:dateCreated
2005-8-4
pubmed:abstractText
Type 3 17beta-hydroxysteroid dehydrogenase (17beta-HSD) is involved in the biosynthesis of androgen testosterone. To produce potent inhibitors of this key steroidogenic enzyme, we prepared a series of androsterone (ADT) derivatives by adding a variety of substituents at position 3. The 3beta-substituted ADT derivatives proved to be good inhibitors (IC(50) = 57-147 nM) with better inhibitory activities obtained for compounds bearing a propyl, s-butyl, cyclohexylalkyl, or phenylalkyl group. With an IC(50) value of 57 nM, the 3beta-phenylmethyl-ADT was 6-fold more potent than ADT, the lead compound, and 13-fold more potent than 4-androstene-3,17-dione, the natural enzyme substrate used itself as inhibitor. The 3alpha-ether-3beta-substituted ADT derivatives had a lower inhibitory activity compared to the 3beta-substituted ADT analogues except for the 3beta-phenylethyl-3alpha-methl-O-ADT (IC(50) = 73 nM), which proved to be a more potent inhibitor than 3beta-phenylethyl-ADT (IC(50) = 99 nM). The results of our study identified potent type 3 17beta-HSD inhibitors for potential use in the treatment of androgen-sensitive diseases.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Aug
pubmed:issn
0022-2623
pubmed:author
pubmed:issnType
Print
pubmed:day
11
pubmed:volume
48
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
5257-68
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed:year
2005
pubmed:articleTitle
Androsterone 3alpha-ether-3beta-substituted and androsterone 3beta-substituted derivatives as inhibitors of type 3 17beta-hydroxysteroid dehydrogenase: chemical synthesis and structure-activity relationship.
pubmed:affiliation
Medicinal Chemistry Division, Oncology and Molecular Endocrinology Research Center, CHUQ-Pavillon CHUL and Université Laval, 2705 Boulevard Laurier, Québec G1V 4G2, Canada.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't