Carbonic anhydrase inhibitors. Inhibition of the fungal β-carbonic anhydrases from Candida albicans and Cryptococcus neoformans with boronic acids

Inhibition of the β-carbonic anhydrases (CAs, EC 4.2.1.1) from the pathogenic fungi Cryptococcus neoformans (Can2) and Candida albicans (Nce103) with a series of aromatic, arylalkenyl- and arylalkylboronic acids was investigated. Aromatic, 4-phenylsubstituted- and 2-naphthylboronic acids were the best Can2 inhibitors, with inhibition constants in the range of 8.5–11.5 μM, whereas arylalkenyl and aryalkylboronic acids showed KIs in the range of 428–3040 μM. Nce103 showed a similar inhibition profile, with the 4-phenylsubstituted- and 2-naphthylboronic acids possessing KIs in the range of 7.8–42.3 μM, whereas the arylalkenyl and aryalkylboronic acids were weaker inhibitors (KIs of 412–5210 μM). The host human enzymes CA I and II were also effectively inhibited by these boronic acids. The B(OH)2 moiety is thus a new zinc-binding group for designing effective inhibitors of the α- and β-CAs.

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