Linked Life Data

18375126

Source:http://linkedlifedata.com/resource/pubmed/id/18375126

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
9
pubmed:dateCreated
2008-5-12
pubmed:abstractText
Even though few steroids are used for the treatment of leukemia, 2beta-(4-methylpiperazinyl)-5alpha-androstane-3alpha,17beta-diol (1) was recently reported for its ability to inhibit the proliferation of human leukemia HL-60 cells. With an efficient procedure that we had developed for the aminolysis of hindered steroidal epoxides, we synthesized a series of 2beta-amino-5alpha-androstane-3alpha,17beta-diol N-derivatives structurally similar to 1. Hence, the opening of 2,3alpha-epoxy-5alpha-androstan-17beta-diol with primary and secondary amines allowed the synthesis of aminosteroids with diverse length, ramification, and functionalization of the 2beta-side chain. Sixty-four steroid derivatives were tested for their capacity to inhibit the proliferation of HL-60 cells; thus obtaining first structure-activity relationship results. Ten aminosteroids with long alkyl chains (7-16 carbons) or bulky groups (diphenyl or adamantyl) have shown antiproliferative activity over 78% at 10microM and superior to that of the lead compound. The 3,3-diphenylpropylamino, 4-nonylpiperazinyl and octylamino derivatives of 5alpha-androstane-3alpha,17beta-diol inhibited the HL-60 cell growth with IC(50) of 3.1, 4.2 and 6.4microM, respectively. They were also found to induce the HL-60 cell differentiation.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
May
pubmed:issn
1464-3391
pubmed:author
pubmed:issnType
Electronic
pubmed:day
1
pubmed:volume
16
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
5062-77
pubmed:meshHeading
pubmed:year
2008
pubmed:articleTitle
Chemical synthesis of 2beta-amino-5alpha-androstane-3alpha,17beta-diol N-derivatives and their antiproliferative effect on HL-60 human leukemia cells.
pubmed:affiliation
Medicinal Chemistry Division, Oncology and Molecular Endocrinology Laboratory, CHUL Research Center (CHUQ-Pavillon CHUL) and Université Laval, 2705 Laurier Boulevard, Que., Canada G1V 4G2.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't