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

Guezel O., Maresca A., Hall R. A., Scozzafava A., Mastrolorenzo A., Muehlschlegel F. A., ...More

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, vol.20, no.8, pp.2508-2511, 2010 (SCI-Expanded) identifier identifier identifier


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 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. (C) 2010 Elsevier Ltd. All rights reserved.