Open AccessCarbonic Anhydrase Inhibition with Benzenesulfonamides and Tetrafluorobenzenesulfonamides Obtained via Click Chemistry
Author(s) -
Nicolino Pala,
Laura Micheletto,
Mario Sechi,
Mayank Aggarwal,
Fabrizio Carta,
Robert McKenna,
Claudiu T. Supuran
Publication year - 2014
Publication title -
acs medicinal chemistry letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.065
H-Index - 66
ISSN - 1948-5875
DOI - 10.1021/ml500196t
Subject(s) - carbonic anhydrase , click chemistry , chemistry , adduct , aryl , gene isoform , sulfonamide , alkyl , cytosol , stereochemistry , benzene , potency , combinatorial chemistry , enzyme , biochemistry , in vitro , organic chemistry , gene
A series of novel benzene- and 2,3,5,6-tetrafluorobenzenesulfonamide was synthesized by using a click chemistry approach starting from azido-substituted sulfonamides and alkynes, incorporating aryl, alkyl, cycloalkyl, and amino-/hydroxy-/halogenoalkyl moieties. The new compounds were medium potency inhibitors of the cytosolic carbonic anhydrase (CA, EC 4.2.1.1) isoforms I and II and low nanomolar/subnanomolar inhibitors of the tumor-associated hCA IX and XII isoforms. The X-ray crystal structure of two such sulfonamides in adduct with hCA II allowed us to understand the factors governing inhibitory power.