Design, synthesis and anti-inflammatory evaluation of PEGylated 4-methyl and 4,8-dimethylcoumarins

Mukesh Pandey, Sakshi Balwani, Pramod K. Sharma, Virinder S. Parmar, Balaram Ghosh, Arthur C. Watterson

Research output: Contribution to journalArticle

15 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)134-140
Number of pages7
JournalEuropean Journal of Pharmaceutical Sciences
Volume39
Issue number1-3
DOIs
StatePublished - Jan 31 2010
Externally publishedYes

Fingerprint

Cell Adhesion Molecules
Anti-Inflammatory Agents
Intercellular Adhesion Molecule-1
Endothelial Cells
Coumarins
Ethylene Glycol
Lipase
Candida
Pharmaceutical Preparations
Endothelium
Polymers
Leukocytes
Cytokines
Inflammation
Therapeutics

Keywords

  • 4,8-Dimethylcoumarin
  • 4-Methylcoumarin
  • Anti-inflammatory
  • Chemo-enzymatic synthesis
  • PEGylated

ASJC Scopus subject areas

  • Pharmaceutical Science

Cite this

Design, synthesis and anti-inflammatory evaluation of PEGylated 4-methyl and 4,8-dimethylcoumarins. / Pandey, Mukesh; Balwani, Sakshi; Sharma, Pramod K.; Parmar, Virinder S.; Ghosh, Balaram; Watterson, Arthur C.

In: European Journal of Pharmaceutical Sciences, Vol. 39, No. 1-3, 31.01.2010, p. 134-140.

Research output: Contribution to journalArticle

Pandey, Mukesh ; 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. In: European Journal of Pharmaceutical Sciences. 2010 ; Vol. 39, No. 1-3. pp. 134-140.
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