Carbonic anhydrase inhibitors: inhibition of isozymes I, II and IX with triazole-linked O-glycosides of benzene sulfonamides

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Title Carbonic anhydrase inhibitors: inhibition of isozymes I, II and IX with triazole-linked O-glycosides of benzene sulfonamides
Author Wilkinson, Brendan Luke; Bornaghi, Laurent; Houston, Todd Ashley; Innocenti, Alessio; Vullo, Daniela; Supuran, Claudiu T.; Poulsen, Sally-Ann
Journal Name Journal of Medicinal Chemistry
Editor Philip S. Portoghese
Year Published 2007
Place of publication Washington DC
Publisher American Chemical Society
Abstract We report the synthesis of a series of benzene sulfonamides containing triazole-O-glycoside tails for evaluation as carbonic anhydrase (CA) inhibitors. These glycoconjugates were synthesized by the 1,3-dipolar cycloaddition reaction of 4-azidobenzenesulfonamide with O-propynyl glycosides. Compounds were assessed for their ability to inhibit the enzymatic activity of the physiologically dominant isozymes hCA I and II and the tumor-associated isozyme hCA IX (h = human). Against hCA I these compounds were either micromolar or low nanomolar inhibitors, while against hCA II and IX inhibition in the range of 6.8–53 nM and 9.7–107 nM, respectively was observed. The most potent inhibitor against hCA IX was the galactose derivative 8 (Ki = 9.7 nM), this is so far the most potent glycoconjugate inhibitor reported for the tumor-associated hCA IX. These carbohydrate-tethered sulfonamides may prove interesting lead candidates to target tumor-associated CA isozymes, wherein the CA domain is located extracellularly.
Peer Reviewed Yes
Published Yes
Publisher URI http://pubs.acs.org/journal/jmcmar
Alternative URI http://dx.doi.org/10.1021/jm061320h
Volume 50
Issue Number 7
Page from 1651
Page to 1657
ISSN 0022-2623
Date Accessioned 2008-01-22
Date Available 2009-12-02T05:35:56Z
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/10072/18264
Publication Type Journal Articles (Refereed Article)
Publication Type Code c1

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