Carbonic anhydrase inhibitors: inhibition of the β-class enzyme from the pathogenic yeast Candida glabrata with sulfonamides, sulfamates and sulfamides.

Abstract:

:The fungal pathogen Candida glabrata encodes for a β-carbonic anhydrase (CA, EC 4.2.1.1), CgNce103, recently discovered. Only anions have been investigated as CgNce103 inhibitors up until now. Here we report the first sulfonamides inhibition study of this enzyme. Simple sulfonamides showed weak or moderate CgNce103 inhibitory properties, whereas acetazolamide, and a series of 4-substituted ureido-benzene-sulfonamides, sulfamates and sulfamides showed effective CgNce103 inhibitory properties, with KIs in the range of 4.1-115 nM, being also ineffective as human CA II inhibitors. As there is significant resistance of C. glabrata clinical isolates to many classical antifungal agents, inhibition of the β-CA from this organism may allow an interesting means of controlling the pathogen growth, eventually leading to antifungals with a novel mechanism of action.

journal_name

Bioorg Med Chem Lett

authors

Vullo D,Leewattanapasuk W,Mühlschlegel FA,Mastrolorenzo A,Capasso C,Supuran CT

doi

10.1016/j.bmcl.2013.02.092

subject

Has Abstract

pub_date

2013-05-01 00:00:00

pages

2647-52

issue

9

eissn

0960-894X

issn

1464-3405

pii

S0960-894X(13)00279-5

journal_volume

23

pub_type

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