Carbonic anhydrase inhibitors. The β-carbonic anhydrases from the fungal pathogens Cryptococcus neoformans and Candida albicans are strongly inhibited by substituted-phenyl-1H-indole-5-sulfonamides

Bioorganic & Medicinal Chemistry Letters
2010.0

Abstract

A series of 2-(hydrazinocarbonyl)-3-substituted-phenyl-1H-indole-5-sulfonamides and 1-({[5-(aminosulfonyl)-3-phenyl-1H-indol-2-yl]carbonyl}amino)-2,4,6 trimethylpyridinium perchlorates possessing various 2-, 3- or 4-substituted phenyl groups with methyl-, halogeno- and methoxy-functionalities, as well as the perfluorophenyl moiety, have been evaluated as inhibitors of the beta-carbonic anhydrases (CAs, EC 4.2.1.1) from the pathogenic fungi Cryptococcus neoformans (Can2) and Candida albicans (CaNce103). Both enzymes were potently inhibited by these sulfonamides, K(I)s in the range of 4.4-118 nM against Can2, and of 5.1-128 against CaNce103, respectively. Minor structural changes in the 3-substituted phenyl moiety contribute significantly to the inhibitory activity. Some of the investigated sulfonamides showed promising selectivity ratios for inhibiting Can2 over the host, human enzymes CA I and II.

DOI： 10.1016/j.bmcl.2010.02.103

Knowledge Graph

Similar Paper

Carbonic anhydrase inhibitors. The β-carbonic anhydrases from the fungal pathogens Cryptococcus neoformans and Candida albicans are strongly inhibited by substituted-phenyl-1H-indole-5-sulfonamides
Bioorganic & Medicinal Chemistry Letters 2010.0
Carbonic anhydrase inhibitors: Inhibition of the β-class enzymes from the fungal pathogens Candida albicans and Cryptococcus neoformans with simple anions
Bioorganic & Medicinal Chemistry Letters 2008.0
Carbonic anhydrase inhibitors. Inhibition of the β-class enzymes from the fungal pathogens Candida albicans and Cryptococcus neoformans with branched aliphatic/aromatic carboxylates and their derivatives
Bioorganic & Medicinal Chemistry Letters 2011.0
Carbonic anhydrase inhibitors. Inhibition of the fungal β-carbonic anhydrases from Candida albicans and Cryptococcus neoformans with boronic acids
Bioorganic & Medicinal Chemistry Letters 2009.0
Carbonic anhydrase inhibitors. Inhibition and homology modeling studies of the fungal β-carbonic anhydrase from Candida albicans with sulfonamides
Bioorganic & Medicinal Chemistry 2009.0
Inhibition of β-carbonic anhydrases with ureido-substituted benzenesulfonamides
Bioorganic & Medicinal Chemistry Letters 2011.0
Carbonic anhydrase inhibitors: Inhibition of the β-class enzyme from the pathogenic yeast Candida glabrata with sulfonamides, sulfamates and sulfamides
Bioorganic & Medicinal Chemistry Letters 2013.0
Carbonic anhydrase inhibitors. Benzenesulfonamides incorporating cyanoacrylamide moieties strongly inhibit Saccharomyces cerevisiae β-carbonic anhydrase
Bioorganic & Medicinal Chemistry Letters 2013.0
Inhibition studies of bacterial, fungal and protozoan β-class carbonic anhydrases with Schiff bases incorporating sulfonamide moieties
Bioorganic & Medicinal Chemistry 2015.0
Carbonic anhydrase inhibitors: Inhibition of the β-class enzyme from the yeast Saccharomyces cerevisiae with sulfonamides and sulfamates
Bioorganic & Medicinal Chemistry 2009.0