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

Abstract

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 CO 2 hydrase activity ( k cat in the range of (3.9–8.0) × 10 5 s −1, and k cat/ K m in the range of (4.3–9.7) × 10 7 M −1 s −1). Can2 was weakly inhibited by cyanide and sulfamic acid ( K Is of 8.22–13.56 mM), while all other anions displayed more potent inhibition. Nce103 was strongly inhibited by cyanide and carbonate ( K Is of 10–11 μM), and weakly inhibited by sulfate, phenylboronic, and phenyl arsonic acid ( K Is 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.