Linked Life Data

19948217

Source:http://linkedlifedata.com/resource/pubmed/id/19948217

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1-3
pubmed:dateCreated
2010-2-3
pubmed:abstractText
Aberrant interaction between the leukocyte and the endothelial cell (EC) resulting from the deregulated expression of cell adhesion molecules (CAMs) on the endothelium results in uncontrolled inflammation leading to various inflammatory disorders. The existing drugs used to modulate the cytokine-induced expression of cell molecules have severe side effects. Therefore, there is an unmet therapeutic need to develop potent and safe drugs to treat inflammatory disorders. In the present study, novel PEGylated and non-PEGylated 4-methyl and 4,8-dimethylcoumarin derivatives were designed, synthesized and, evaluated for ICAM-1 inhibitory activity. The PEGylated coumarins were synthesized in two different ways. In the first approach, diesters of 4-methyl and 4,8-dimethylcoumarin were co-polymerized, separately with poly(ethylene glycol) using Candida antarctica lipase under solventless conditions. In the other approach, 4-methyl and 4,8-dimethylcoumarins were suitably converted to their bromo analogues and were tethered to already synthesized PEGylated polymers. Synthesized derivatives were evaluated for anti-inflammatory activities with respect to their ability to inhibit the TNF-alpha induced ICAM-1 (intercellular cell adhesion molecule-1) on human endothelial cells. It was found that PEGylated 4-methyl and 4,8-dimethylcoumarin derivatives were more effective than their non-PEGylated analogues to inhibit ICAM-1 expression. The present study opens new vista for PEGylated non-steroidal anti-inflammatory compounds and their further investigations.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jan
pubmed:issn
1879-0720
pubmed:author
pubmed:copyrightInfo
Copyright 2009 Elsevier B.V. All rights reserved.
pubmed:issnType
Electronic
pubmed:day
31
pubmed:volume
39
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
134-40
pubmed:meshHeading
pubmed:year
2010
pubmed:articleTitle
Design, synthesis and anti-inflammatory evaluation of PEGylated 4-methyl and 4,8-dimethylcoumarins.
pubmed:affiliation
Institute of Nano-science and Engineering Technology, University of Massachusetts Lowell, One University Avenue Lowell, MA 01854, USA.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't