Linked Life Data

17390157

Source:http://linkedlifedata.com/resource/pubmed/id/17390157

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
5
pubmed:dateCreated
2007-4-26
pubmed:abstractText
Microsomal prostaglandin E(2) synthase (mPGES-1) has been identified recently as a novel target for treating pain and inflammation. The aim of this study is to understand the binding affinities of reported inhibitors for mPGES-1 and further to design potential new mPGES-1 inhibitors. 3D-QSAR-CoMFA (comparative molecular field analysis) and CoMSIA (comparative molecular similarity indices analysis) - techniques were employed on a series of indole derivatives that act as selective mPGES-1 inhibitors. The lowest energy conformer of the most active compound obtained from systematic conformational search was used as a template for the alignment of 32 compounds. The models obtained were used to predict the activities of the test set of eight compounds, and the predicted values were in good agreement with the experimental results. The 3D-QSAR models derived from the training set of 24 compounds were all statistically significant (CoMFA; q (2) = 0.89, r (2) = 0.95, [Formula: see text], [Formula: see text] and CoMSIA; q (2) = 0.84, r (2) = 0.93, [Formula: see text], [Formula: see text]). Contour plots generated for the CoMFA and CoMSIA models reveal useful clues for improving the activity of mPGES-1 inhibitors. In particular, substitutions of an electronegative fluorine atom or a bulky hydrophilic phenoxy group at the meta or para positions of the biphenyl rings might improve inhibitory activity. A plausible binding mode between the ligands and mPGES-1 is also proposed.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
May
pubmed:issn
0948-5023
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
13
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
601-10
pubmed:meshHeading
pubmed:year
2007
pubmed:articleTitle
3D-QSAR study of microsomal prostaglandin E2 synthase (mPGES-1) inhibitors.
pubmed:affiliation
Biochemicals Research Center, Life Science Division, Korea Institute of Science and Technology, Cheongryang, Seoul, South Korea. asanjuan@kist.re.kr
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't