Metadata of CSIR Papers
View Archive Info| Field | Value | |
| Creator |
Pandey, MK
Balwani, S Sharma, PK Parmar, VS Ghosh, B Watterson, AC |
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| Subject |
Pharmacology & Pharmacy
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| Description |
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. (C) 2009 Elsevier B.V. All rights reserved.
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| Publisher |
ELSEVIER SCIENCE BVAMSTERDAMPO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
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| Date |
2011-09-20T12:07:12Z
2011-09-20T12:07:12Z 2010 |
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| Type |
Article
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| Identifier |
EUROPEAN JOURNAL OF PHARMACEUTICAL SCIENCES
0928-0987 http://hdl.handle.net/123456789/13148 |
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| Language |
English
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