Design, synthesis and anti-inflammatory evaluation of PEGylated 4-methyl and 4, 8-dimethylcoumarins
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-ind...
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ftindianacasci:oai:repository.ias.ac.in:66008 2023-05-15T13:46:14+02:00 Design, synthesis and anti-inflammatory evaluation of PEGylated 4-methyl and 4, 8-dimethylcoumarins Pandey, Mukesh K. Balwani, Sakshi Sharma, Pramod K. Parmar, Virinder S. Ghosh, Balaram Watterson, Arthur C. 2010-01-31 http://repository.ias.ac.in/66008/ http://www.sciencedirect.com/science/article/pii/S0928098709003509 unknown Elsevier Science Pandey, Mukesh K. Balwani, Sakshi Sharma, Pramod K. Parmar, Virinder S. Ghosh, Balaram Watterson, Arthur C. (2010) Design, synthesis and anti-inflammatory evaluation of PEGylated 4-methyl and 4, 8-dimethylcoumarins European Journal of Pharmaceutical Sciences, 39 (1-3). pp. 134-140. ISSN 0928-0987 QH301 Biology Article PeerReviewed 2010 ftindianacasci 2013-01-20T12:30:25Z 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-α 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. Article in Journal/Newspaper Antarc* Antarctica Indian Academy of Sciences: Publication of Fellows |
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QH301 Biology |
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QH301 Biology Pandey, Mukesh K. Balwani, Sakshi Sharma, Pramod K. Parmar, Virinder S. Ghosh, Balaram Watterson, Arthur C. Design, synthesis and anti-inflammatory evaluation of PEGylated 4-methyl and 4, 8-dimethylcoumarins |
topic_facet |
QH301 Biology |
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-α 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. |
format |
Article in Journal/Newspaper |
author |
Pandey, Mukesh K. Balwani, Sakshi Sharma, Pramod K. Parmar, Virinder S. Ghosh, Balaram Watterson, Arthur C. |
author_facet |
Pandey, Mukesh K. Balwani, Sakshi Sharma, Pramod K. Parmar, Virinder S. Ghosh, Balaram Watterson, Arthur C. |
author_sort |
Pandey, Mukesh K. |
title |
Design, synthesis and anti-inflammatory evaluation of PEGylated 4-methyl and 4, 8-dimethylcoumarins |
title_short |
Design, synthesis and anti-inflammatory evaluation of PEGylated 4-methyl and 4, 8-dimethylcoumarins |
title_full |
Design, synthesis and anti-inflammatory evaluation of PEGylated 4-methyl and 4, 8-dimethylcoumarins |
title_fullStr |
Design, synthesis and anti-inflammatory evaluation of PEGylated 4-methyl and 4, 8-dimethylcoumarins |
title_full_unstemmed |
Design, synthesis and anti-inflammatory evaluation of PEGylated 4-methyl and 4, 8-dimethylcoumarins |
title_sort |
design, synthesis and anti-inflammatory evaluation of pegylated 4-methyl and 4, 8-dimethylcoumarins |
publisher |
Elsevier Science |
publishDate |
2010 |
url |
http://repository.ias.ac.in/66008/ http://www.sciencedirect.com/science/article/pii/S0928098709003509 |
genre |
Antarc* Antarctica |
genre_facet |
Antarc* Antarctica |
op_relation |
Pandey, Mukesh K. Balwani, Sakshi Sharma, Pramod K. Parmar, Virinder S. Ghosh, Balaram Watterson, Arthur C. (2010) Design, synthesis and anti-inflammatory evaluation of PEGylated 4-methyl and 4, 8-dimethylcoumarins European Journal of Pharmaceutical Sciences, 39 (1-3). pp. 134-140. ISSN 0928-0987 |
_version_ |
1766238729549119488 |