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 Lettjournal_title
Bioorganic & medicinal chemistry lettersauthors
Vullo D,Leewattanapasuk W,Mühlschlegel FA,Mastrolorenzo A,Capasso C,Supuran CTdoi
10.1016/j.bmcl.2013.02.092subject
Has Abstractpub_date
2013-05-01 00:00:00pages
2647-52issue
9eissn
0960-894Xissn
1464-3405pii
S0960-894X(13)00279-5journal_volume
23pub_type
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