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Carbonic anhydrase inhibitors: inhibition of the β-class enzymes from the fungal pathogens Candida albicans and Cryptococcus neoformans with simple anions

Titelangaben

Innocenti, Alessio ; Mühlschlegel, Fritz A. ; Hall, Rebecca A. ; Steegborn, Clemens ; Scozzafava, Andrea ; Supuran, Claudiu T.:
Carbonic anhydrase inhibitors: inhibition of the β-class enzymes from the fungal pathogens Candida albicans and Cryptococcus neoformans with simple anions.
In: Bioorganic & Medicinal Chemistry Letters. Bd. 18 (2008) Heft 18 . - S. 5066-5070.
ISSN 1464-3405
DOI: https://doi.org/10.1016/j.bmcl.2008.07.122

Abstract

The catalytic activity and inhibition of the beta-carbonic anhydrases (CAs, EC 4.2.1.1) from the pathogenic fungi Candida albicans (Nce103) and Cryptococcus neoformans (Can2) with inorganic anions such as halogenides, pseudohalogenides, bicarbonate, carbonate, nitrate, nitrite, hydrogen sulfide, bisulfite, perchlorate, sulfate were investigated. The two enzymes showed appreciable CO(2) hydrase activity (k(cat) in the range of (3.9-8.0)x10(5)s(-1), and k(cat)/K(m) in the range of (4.3-9.7)x10(7)M(-1)s(-1)). Can2 was weakly inhibited by cyanide and sulfamic acid (K(I)s of 8.22-13.56 mM), while all other anions displayed more potent inhibition. Nce103 was strongly inhibited by cyanide and carbonate (K(I)s of 10-11 microM), and weakly inhibited by sulfate, phenylboronic, and phenyl arsonic acid (K(I)s of 14.15-30.85 mM). These data demonstrate that pathogenic, fungal beta-CAs may be targets for the development of antifungals that have a novel mechanism of action.

Weitere Angaben

Publikationsform: Artikel in einer Zeitschrift
Begutachteter Beitrag: Ja
Zusätzliche Informationen: PubMed-ID: 18723348
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 12:09
Letzte Änderung: 25 Apr 2022 12:26
URI: https://eref.uni-bayreuth.de/id/eprint/10306