Linked Life Data

15165135

Source:http://linkedlifedata.com/resource/pubmed/id/15165135

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
5
pubmed:dateCreated
2004-5-28
pubmed:abstractText
The transcription factor hypoxia-inducible factor-1 (HIF-1) is a key regulator of tumor cell adaptation and survival under hypoxic conditions. Selective HIF-1 inhibitors represent an important new class of potential molecular-targeted antitumor therapeutic agents. Extracts of plants and marine organisms were evaluated using a T47D human breast tumor cell-based reporter assay for HIF-1 inhibitors. Bioassay-guided fractionation of the lipid extract of Saururus cernuus resulted in the isolation of manassantin B (1) and a new compound, 4-O-demethylmanassantin B (2). The structure of 2 was determined spectroscopically. The absolute configurations of manassantin-type dineolignans have not been previously reported. Therefore, the absolute configurations of the chiral centers in each side chain were deduced from spectroscopic analysis of the Mosher MTPA ester derivatives of 1. Both 1 and 2 are among the most potent small molecule HIF-1 inhibitors discovered, to date, with IC(50) values of 3 and 30 nM, respectively. Compounds 1 and 2 selectively inhibited hypoxia-activated HIF-1 in contrast to iron chelator-activated HIF-1. Compounds 1 and 2 also inhibited hypoxic induction of the angiogenic factor VEGF. Further study revealed that 1 selectively blocked the induction of HIF-1alpha protein, the oxygen regulated HIF-1 subunit that determines HIF-1 activity.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
May
pubmed:issn
0163-3864
pubmed:author
pubmed:issnType
Print
pubmed:volume
67
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
767-71
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed-meshheading:15165135-Anoxia, pubmed-meshheading:15165135-Antineoplastic Agents, Phytogenic, pubmed-meshheading:15165135-DNA-Binding Proteins, pubmed-meshheading:15165135-Dose-Response Relationship, Drug, pubmed-meshheading:15165135-Enzyme-Linked Immunosorbent Assay, pubmed-meshheading:15165135-Furans, pubmed-meshheading:15165135-Hypoxia-Inducible Factor 1, pubmed-meshheading:15165135-Inhibitory Concentration 50, pubmed-meshheading:15165135-Lignans, pubmed-meshheading:15165135-Nuclear Proteins, pubmed-meshheading:15165135-Plants, Medicinal, pubmed-meshheading:15165135-Saururaceae, pubmed-meshheading:15165135-Stereoisomerism, pubmed-meshheading:15165135-Structure-Activity Relationship, pubmed-meshheading:15165135-Transcription Factors, pubmed-meshheading:15165135-Vascular Endothelial Growth Factor A
pubmed:year
2004
pubmed:articleTitle
Molecular-targeted antitumor agents: the Saururus cernuus dineolignans manassantin B and 4-O-demethylmanassantin B are potent inhibitors of hypoxia-activated HIF-1.
pubmed:affiliation
Department of Pharmacognosy, National Center for Natural Products Research, and Research Institute of Pharmaceutical Sciences, School of Pharmacy, University of Mississippi, University, Mississippi 38677-1848, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, Non-P.H.S.