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Carbonic anhydrase inhibitors : Inhibition and homology modeling studies of the fungal beta-carbonic anhydrase from Candida albicans with sulfonamides.

Title data

Innocenti, Alessio ; Hall, Rebecca A. ; Schlicker, Christine ; Scozzafava, Andrea ; Steegborn, Clemens ; Mühlschlegel, Fritz A. ; Supuran, Claudiu T.:
Carbonic anhydrase inhibitors : Inhibition and homology modeling studies of the fungal beta-carbonic anhydrase from Candida albicans with sulfonamides.
In: Bioorganic & Medicinal Chemistry. Vol. 17 (1 July 2009) Issue 13 . - pp. 4503-4509.
ISSN 1464-3391
DOI: https://doi.org/10.1016/j.bmc.2009.05.002

Abstract in another language

The beta-carbonic anhydrase (CA, EC 4.2.1.1) from the fungal pathogen Candida albicans (Nce103) is involved in a CO(2) sensing pathway critical for the pathogen life cycle and amenable to drug design studies. Herein we report an inhibition study of Nce103 with a library of sulfonamides and one sulfamate, showing that Nce103, similarly to the related enzyme from Cryptococcus neoformans Can2, is inhibited by these compounds with K(I)s in the range of 132 nM-7.6 microM. The best Nce103 inhibitors were acetazolamide, methazolamide, bromosulfanilamide, and 4-hydroxymethylbenzenesulfonamide (K(I)s<500 nM). A homology model was generated for Nce103 based on the crystal structure of Can2. The model shows that compounds with zinc-binding groups incorporating less polar moieties and compact scaffolds generate stronger Nce103 inhibitors, whereas highly polar zinc-binding groups and bulkier compounds appear more promising for the specific inhibition of Can2. Such compounds may be useful for the design of antifungal agents possessing a new mechanism of action.

Further data

Item Type: Article in a journal
Refereed: Yes
Additional notes: PubMed-ID: 19450983
Institutions of the University: Faculties > Faculty of Biology, Chemistry and Earth Sciences > Department of Chemistry > Chair Biochemistry > Chair Biochemistry - Univ.-Prof. Dr. Clemens Steegborn
Faculties
Faculties > Faculty of Biology, Chemistry and Earth Sciences
Faculties > Faculty of Biology, Chemistry and Earth Sciences > Department of Chemistry
Faculties > Faculty of Biology, Chemistry and Earth Sciences > Department of Chemistry > Chair Biochemistry
Result of work at the UBT: No
DDC Subjects: 500 Science > 540 Chemistry
Date Deposited: 16 Apr 2015 12:20
Last Modified: 16 Apr 2015 12:20
URI: https://eref.uni-bayreuth.de/id/eprint/10310