S-glycosyl primary sulfonamides-A new structural class for selective inhibition of cancer-associated carbonic anhydrases

There are no files associated with this record.

Title S-glycosyl primary sulfonamides-A new structural class for selective inhibition of cancer-associated carbonic anhydrases
Author Lopez, Marie; Paul, Blessy Abraham; Hofmann, Andreas; Morizzi, Julia; Wu, Quoc K.; Charman, Susan A.; Innocenti, Alessio; Vullo, Daniela; Supuran, Claudiu T.; Poulsen, Sally-Ann
Journal Name Journal of Medicinal Chemistry
Year Published 2009
Place of publication United States
Publisher American Chemical Society
Abstract In this paper, we present a new class of carbonic anhydrase (CA) inhibitor that was designed to selectively target the extracellular domains of the cancer-relevant CA isozymes. The aromatic moiety of the classical zinc binding sulfonamide CA inhibitors is absent from these compounds and instead they incorporate a hydrophilic mono- or disaccharide fragment directly attached to the sulfonamide group to give S-glycosyl primary sulfonamides (1−10). The inhibition properties of these compounds at the physiologically abundant human CA isozymes I and II and cancer-associated IX and XII were determined, and all compounds had moderate potency with Kis in the micromolar range. We present the crystal structures of anomeric sulfonamides 4, 7, and 10 and the sugar sulfamate drug topiramate in complex with human recombinant CA II. From these structures, we have obtained valuable insights into ligand−protein interactions of these novel carbohydrate-based sulfonamides with CA.
Peer Reviewed Yes
Published Yes
Publisher URI http://pubs.acs.org/journal/jmcmar
Alternative URI http://dx.doi.org/10.1021/jm900914e
Copyright Statement Copyright 2009 American Chemical Society. Self-archiving of the author-manuscript version is not yet supported by this publisher. Please refer to the journal link for access to the definitive, published version or contact the authors for more information.
Volume 52
Issue Number 20
Page from 6421
Page to 6432
ISSN 0022-2623
Date Accessioned 2009-10-18
Language en_AU
Research Centre Eskitis Institute for Drug Discovery
Faculty Faculty of Science, Environment, Engineering and Technology
Subject Structural Chemistry and Spectroscopy
URI http://hdl.handle.net/10072/28013
Publication Type Journal Articles (Refereed Article)
Publication Type Code c1

Show simple item record

Griffith University copyright notice