A novel class of carbonic anhydrase inhibitors: glycoconjugate benzene sulfonamides prepared by "click-tailing"
Author(s)
Wilkinson, Brendan L
Bornaghi, Laurent F
Houston, Todd A
Innocenti, Alessio
Supuran, Claudiu T
Poulsen, Sally-Ann
Griffith University Author(s)
Year published
2006
Metadata
Show full item recordAbstract
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 ...
View more >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.
View less >
View more >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.
View less >
Journal Title
Journal of Medicinal Chemistry
Volume
49
Issue
22
Publisher URI
Copyright Statement
© 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.
Subject
Medicinal and biomolecular chemistry
Organic chemistry
Pharmacology and pharmaceutical sciences