Inhibition of bacterial α-, β- and γ-class carbonic anhydrases with selenazoles incorporating benzenesulfonamide moieties

J Enzyme Inhib Med Chem. 2019 Dec;34(1):244-249. doi: 10.1080/14756366.2018.1547287.

Abstract

A series of benzenesulfonamides incorporating selenazoles with diverse substitution patterns were investigated as inhibitors of six bacterial carbonic anhydrases (CAs, EC 4.2.1.1) from bacterial pathogens, such as Helicobacter pylori (hpCAα was the investigated enzyme), Vibrio cholerae (all the three CAs from this pathogen were considered, VchCAα, VchCAβ and VchCAγ) and Burkholderia pseudomallei (with its two CAs, BpsCAβ and BpsCAγ). All these sulfonamides were effective CA inhibitors, with potencies in the low micromolar or submicromolar range, making them attractive as lead compounds for designing antibacterials with a novel mechanism of action, which could counteract the extensive resistance problem observed with many clinically used antibiotics.

Keywords: Carbonic anhydrase; bacterial enzymes.

MeSH terms

  • Benzenesulfonamides
  • Burkholderia pseudomallei / enzymology*
  • Carbonic Anhydrase Inhibitors / chemical synthesis
  • Carbonic Anhydrase Inhibitors / chemistry
  • Carbonic Anhydrase Inhibitors / pharmacology*
  • Carbonic Anhydrases / metabolism*
  • Dose-Response Relationship, Drug
  • Helicobacter pylori / enzymology*
  • Molecular Structure
  • Organoselenium Compounds / chemistry
  • Organoselenium Compounds / pharmacology*
  • Structure-Activity Relationship
  • Sulfonamides / chemistry
  • Sulfonamides / pharmacology*
  • Vibrio cholerae / enzymology*

Substances

  • Carbonic Anhydrase Inhibitors
  • Organoselenium Compounds
  • Sulfonamides
  • Carbonic Anhydrases

Grants and funding

This work was supported by a grant of the Romanian Ministery of Research and Innovation, CNCS – UEFISCDI, project number PN-III-P4-ID-PCCF-2016–0050, within PNCDI III.