Article ID Journal Published Year Pages File Type
1371188 Bioorganic & Medicinal Chemistry Letters 2011 6 Pages PDF
Abstract

The 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 25 branched aliphatic and aromatic carboxylates has been investigated. Human isoforms hCA I and II were also included in the study for comparison. Aliphatic carboxylates were generally millimolar hCA I and II inhibitors and low micromolar/submicromolar β-CA inhibitors. Aromatic carboxylates were micromolar inhibitors of the four enzymes but some of them showed low nanomolar activity against the fungal pathogenic enzymes. 4-Hydroxy- and 4-methoxy-benzoate inhibited Can2 with KIs of 9.5–9.9 nM. The methyl esters, hydroxamates, hydrazides and carboxamides of some of these derivatives were also effective inhibitors of the α- and β-CAs investigated here.

Graphical abstractKI = 7.61 μM (hCA I); 7.28 μM (hCA II); 9.5 nM (Can2); 110 nM (Nce103).Figure optionsDownload full-size imageDownload as PowerPoint slide

Related Topics
Physical Sciences and Engineering Chemistry Organic Chemistry
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