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

Abstract

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 K Is in the range of 428–3040 μM. Nce103 showed a similar inhibition profile, with the 4-phenylsubstituted- and 2-naphthylboronic acids possessing K Is in the range of 7.8–42.3 μM, whereas the arylalkenyl and aryalkylboronic acids were weaker inhibitors ( K Is 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.