Carbonic anhydrase inhibitors: Inhibition of the β-class enzyme from the pathogenic yeast Candida glabrata with sulfonamides,sulfamates and sulfamides |
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| Authors: | Daniela Vullo Worraanong Leewattanapasuk Fritz A Mühlschlegel Antonio Mastrolorenzo Clemente Capasso Claudiu T Supuran |
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| Institution: | 1. Università degli Studi di Firenze, Laboratorio di Chimica Bioinorganica, Rm. 188, Via della Lastruccia 3, I-50019 Sesto Fiorentino, Florence, Italy;2. School of Biosciences, University of Kent, Canterbury, Kent CT2 7NJ, United Kingdom;3. Università degli Studi di Firenze, Centro MTS, Dipartimento di Dermatologia, Firenze, Italy;4. Istituto di Biochimica delle Proteine—CNR, Via P. Castellino 111, 80131 Napoli, Italy;5. Università degli Studi di Firenze, NEUROFARBA Dept., Sezione di Scienze Farmaceutiche e Nutraceutiche, Via Ugo Schiff 6, I-50019 Sesto Fiorentino, Florence, Italy |
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| 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. |
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