Wilkinson, Brendan

Bornaghi, Laurent F

Houston, Todd A

Innocenti, Alessio

Supuran, Claudiu T

Poulsen, Sally-Ann

2006

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.

Journal of Medicinal Chemistry, 49(22), p. 6539-6548

1520-4804

0022-2623

https://hdl.handle.net/1959.11/22910

en

American Chemical Society

A Novel Class of Carbonic Anhydrase Inhibitors: Glycoconjugate Benzene Sulfonamides Prepared by "Click-Tailing"

Journal Article

Publication