The University of Dublin | Trinity College -- Ollscoil Átha Cliath | Coláiste na Tríonóide
Trinity's Access to Research Archive
Home :: Log In :: Submit :: Alerts ::

TARA >
Administrative Staff Authors  >
Administrative Staff Authors (Scholarly Publications) >

Please use this identifier to cite or link to this item: http://hdl.handle.net/2262/60695

Title: A double prodrug system for colon targeting of benzenesulfonamide COX-2 inhibitors
Author: WINDLE, HENRY
GILMER, JOHN FRANCIS
KELLEHER, DERMOT P
KEOGH, BRIAN
REILLY, MARY
Sponsor: 
Name Grant Number
IP/2007/503

Author's Homepage: http://people.tcd.ie/kellehdp
http://people.tcd.ie/hjwindle
http://people.tcd.ie/gilmerjf
http://people.tcd.ie/keoghbr
http://people.tcd.ie/reillym3
Keywords: Oncology
Pharmacology
COX-2 inhibitor
Colon cancer
Issue Date: 2011
Citation: Marquez Ruiz JF, Kedziora K, Keogh B, Maguire J, Reilly M, Windle HJ, Kelleher D, Gilmer JF, A double prodrug system for colon targeting of benzenesulfonamide COX-2 inhibitors, Bioorganic & Medicinal Chemistry Letters, 21, 22, 2011, 6636-6640
Series/Report no.: Bioorganic & Medicinal Chemistry Letters
21
22
Abstract: The design, synthesis and delivery potential of a new type of benzenesulfonamide cyclo-oxygenase-2 (COX-2) inhibitor prodrug is investigated using celecoxib. The approach involves a double prodrug that is activated first by azoreductases and then by cyclization triggering drug release. We studied the intramolecular aminolysis of the acylsulfonamide. The cyclization was surprisingly rapid at physiological pH and very fast at pH 5. The prodrug is activated specifically under conditions found in the colon but highly stable in the presence of human and rodent intestinal extracts. Finally, the prototype with celecoxib was transported much more slowly in the Caco-2 transepithelial model than the parent. The design therefore shows significant promise for the site specific delivery of benzenesulfonamide COX-2 inhibitors to the colon.
Description: PUBLISHED
URI: http://hdl.handle.net/2262/60695
Related links: http://dx.doi.org/10.1016/j.bmcl.2011.09.071
Appears in Collections:Administrative Staff Authors (Scholarly Publications)

Files in This Item:

File Description SizeFormat
A double prodrug system for colon targeting of benzenesulfonamide COX-2 inhibitors.pdfPublished (author's copy) - Peer Reviewed303.35 kBAdobe PDFView/Open


This item is protected by original copyright


Please note: There is a known bug in some browsers that causes an error when a user tries to view large pdf file within the browser window. If you receive the message "The file is damaged and could not be repaired", please try one of the solutions linked below based on the browser you are using.

Items in TARA are protected by copyright, with all rights reserved, unless otherwise indicated.

 

Valid XHTML 1.0! DSpace Software Copyright © 2002-2010  Duraspace - Feedback