A novel class of carbonic anhydrase inhibitors: glycoconjugate benzene sulfonamides prepared by "click-tailing"

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Title A novel class of carbonic anhydrase inhibitors: glycoconjugate benzene sulfonamides prepared by "click-tailing"
Author Wilkinson, Brendan Luke; Bornaghi, Laurent; Houston, Todd Ashley; Innocenti, Alessio; Supuran, Claudiu T.; Poulsen, Sally-Ann
Journal Name Journal of Medicinal Chemistry
Editor Philip S. Portoghese
Year Published 2006
Place of publication Columbus, Ohio
Publisher American Chemical Society
Abstract Aryl and heteroaryl sulfonamides (ArSO2NH2) are therapeutically used to inhibit the catalytic activity of carbonic anhydrases (CAs). Using a “click-tail” approach a novel class of glycoconjugate benzene sulfonamides have been synthesized that contain diverse carbohydrate−triazole tails. These compounds were assessed for their ability to inhibit three human CA isozymes in vitro: cytosolic hCA I and hCA II and transmembrane, tumor-associated hCA IX. This isozyme has a minimal expression in normal tissue but is overexpressed in hypoxic tumors and its inhibition is a current approach toward new cancer therapies. The qualitative structure−activity for all derivatives demonstrated that the stereochemical diversity present within the carbohydrate tails effectively interrogated the CA active site topology, to generate several inhibitors that were potent and selective toward hCA IX, an important outcome in the quest for potential cancer therapy applications based on CA inhibition.
Peer Reviewed Yes
Published Yes
Publisher URI http://pubs.acs.org/journal/jmcmar?cookieSet=1
Alternative URI http://dx.doi.org/10.1021/jm060967z
Copyright Statement Copyright 2006 American Chemical Society. Self-archiving of the author-manuscript version is not yet supported by this publisher. Please use the hypertext link to access the journal's website or contact the author for more information. Please refer to the journal for the definitive published version.
Volume 49
Issue Number 22
Edition 2006
Page from 6539
Page to 6548
ISSN 0022-2623
Date Accessioned 2007-02-02
Language en_AU
Research Centre Eskitis Institute for Drug Discovery; Institute for Glycomics
Faculty Faculty of Science, Environment, Engineering and Technology
Subject PRE2009-Biological and Medical Chemistry
URI http://hdl.handle.net/10072/11308
Publication Type Journal Articles (Refereed Article)
Publication Type Code c1

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