Literatur vom gleichen Autor/der gleichen Autor*in
plus bei Google Scholar

Bibliografische Daten exportieren
 

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

Titelangaben

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 β-carbonic anhydrase from Candida albicans with sulfonamides.
In: Bioorganic & Medicinal Chemistry. Bd. 17 (2009) Heft 13 . - S. 4503-4509.
ISSN 0968-0896
DOI: https://doi.org/10.1016/j.bmc.2009.05.002

Abstract

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.

Weitere Angaben

Publikationsform: Artikel in einer Zeitschrift
Begutachteter Beitrag: Ja
Zusätzliche Informationen: PubMed-ID: 19450983
Institutionen der Universität: Fakultäten > Fakultät für Biologie, Chemie und Geowissenschaften > Fachgruppe Chemie > Lehrstuhl Biochemie > Lehrstuhl Biochemie I - Proteinbiochemie der Signaltransduktion - Univ.-Prof. Dr. Clemens Steegborn
Fakultäten
Fakultäten > Fakultät für Biologie, Chemie und Geowissenschaften
Fakultäten > Fakultät für Biologie, Chemie und Geowissenschaften > Fachgruppe Chemie
Fakultäten > Fakultät für Biologie, Chemie und Geowissenschaften > Fachgruppe Chemie > Lehrstuhl Biochemie
Titel an der UBT entstanden: Nein
Themengebiete aus DDC: 500 Naturwissenschaften und Mathematik > 540 Chemie
Eingestellt am: 16 Apr 2015 12:20
Letzte Änderung: 25 Apr 2022 12:24
URI: https://eref.uni-bayreuth.de/id/eprint/10310