Carbonic anhydrase inhibitors: Inhibition of the β-class enzyme from the pathogenic yeast Candida glabrata with sulfonamides, sulfamates and sulfamides

https://doi.org/10.1016/j.bmcl.2013.02.092Get rights and content

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.

Section snippets

Acknowledgments

This research was financed in part by two 7th FP EU projects (METOXIA and DYNANO) to CTS.

References and notes (23)

  • T. Klengel et al.

    Curr. Biol.

    (2005)
    Y.S. Bahn et al.

    Curr. Biol.

    (2005)
  • E.G. Mogensen et al.

    Eukaryot. Cell

    (2006)
    Y.S. Bahn et al.

    Curr. Opin. Microbiol.

    (2006)
  • U.M. Ohndorf et al.

    Crystallographic Studies on Carbonic Anhydrases from Fungal Pathogens for Structure-Assisted Drug Development

  • F. Cottier et al.

    Bioorg. Med. Chem.

    (2013)
  • F. Cottier et al.

    PLoS Pathog.

    (2012)
    S. Isik et al.

    Bioorg. Med. Chem. Lett.

    (2008)
    S.M. Monti et al.

    Bioorg. Med. Chem. Lett.

    (2012)
  • S.A. Zimmerman et al.

    Curr. Top. Med. Chem.

    (2007)
    C.T. Supuran

    Nat. Rev. Drug Disc.

    (2008)
    C.T. Supuran

    J. Enzyme Inhib. Med. Chem.

    (2012)
    F. Bootorabi et al.

    J. Enzyme Inhib. Med. Chem.

    (2011)
    O. Ozensoy et al.

    J. Enzyme Inhib. Med. Chem.

    (2011)
    S. Kolayli et al.

    J. Enzyme Inhib. Med. Chem.

    (2011)
    H. Sahin et al.

    J. Enzyme Inhib. Med. Chem.

    (2011)
  • A. Innocenti et al.

    Bioorg. Med. Chem. Lett.

    (2008)
  • A. Innocenti et al.

    Bioorg. Med. Chem.

    (2009)
    A. Innocenti et al.

    Bioorg. Med. Chem.

    (2009)
  • F. Pacchiano et al.

    Chem. Commun.

    (2010)
  • L. Syrjänen et al.

    BMC Biochem.

    (2010)
    A. Maresca et al.

    J. Enzyme Inhib. Med. Chem.

    (2013)
  • R.A. Hall et al.

    Fungal and Nematode Carbonic Anhydrases: Their Inhibition in Drug Design

  • Cited by (43)

    • Carbonic anhydrases from pathogens: Fungal carbonic anhydrases and their inhibitors as potential antifungal agents

      2019, Carbonic Anhydrases: Biochemistry and Pharmacology of an Evergreen Pharmaceutical Target
    View all citing articles on Scopus
    View full text