Carbonic anhydrase inhibitors: Inhibition of the β-class enzymes from the fungal pathogens Candida albicans and Cryptococcus neoformans with simple anions

The catalytic activity and inhibition of the β-carbonic anhydrases (CAs, EC 4.2.1.1) from the pathogenic fungi Candida albicans (Nce103) and Cryptococcus neoformans (Can2) with inorganic anions such as halogenides, pseudohalogenides, bicarbonate, carbonate, nitrate, nitrite, hydrogen sulfide, bisulfite, perchlorate, sulfate were investigated. The two enzymes showed appreciable CO2 hydrase activity (kcat in the range of (3.9–8.0) × 105 s−1, and kcat/Km in the range of (4.3–9.7) × 107 M−1 s−1). Can2 was weakly inhibited by cyanide and sulfamic acid (KIs of 8.22–13.56 mM), while all other anions displayed more potent inhibition. Nce103 was strongly inhibited by cyanide and carbonate (KIs of 10–11 μM), and weakly inhibited by sulfate, phenylboronic, and phenyl arsonic acid (KIs of 14.15–30.85 mM). These data demonstrate that pathogenic, fungal β-CAs may be targets for the development of antifungals that have a novel mechanism of action.

Graphical abstractFigure optionsDownload full-size imageDownload as PowerPoint slide