Sulfonamide inhibition studies of the β-carbonic anhydrase from the newly discovered bacterium Enterobacter sp. B13

Bioorg Med Chem Lett. 2016 Apr 1;26(7):1821-6. doi: 10.1016/j.bmcl.2016.02.032. Epub 2016 Feb 16.

Abstract

The genome of the newly identified bacterium Enterobacter sp. B13 encodes for a β-class carbonic anhydrases (CAs, EC 4.2.1.1), EspCA. This enzyme was recently cloned, and characterized kinetically by this group (J. Enzyme Inhib. Med. Chem. 2016, 31). Here we report an inhibition study with sulfonamides and sulfamates of this enzyme. The best EspCA inhibitors were some sulfanylated sulfonamides with elongated molecules, metanilamide, 4-aminoalkyl-benzenesulfonamides, acetazolamide, and deacetylated methazolamide (KIs in the range of 58.7-96.5nM). Clinically used agents such as methazolamide, ethoxzolamide, dorzolamide, brinzolamide, benzolamide, zonisamide, sulthiame, sulpiride, topiramate and valdecoxib were slightly less effective inhibitors (KIs in the range of 103-138nM). Saccharin, celecoxib, dichlorophenamide and many simple benzenesulfonamides were even less effective as EspCA inhibitors, with KIs in the range of 384-938nM. Identification of effective inhibitors of this bacterial enzyme may lead to pharmacological tools useful for understanding the physiological role(s) of the β-class CAs in bacterial pathogenicity/virulence.

Keywords: Carbonic anhydrase; Enterobacter spp. B13; Inhibitors; Metalloenzymes; Pathogenic bacteria; Sulfonamide.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetazolamide / chemistry
  • Acetazolamide / pharmacology
  • Carbonic Anhydrase I / antagonists & inhibitors*
  • Carbonic Anhydrase I / metabolism
  • Carbonic Anhydrase Inhibitors / chemistry*
  • Carbonic Anhydrase Inhibitors / pharmacology*
  • Enterobacter / drug effects
  • Enterobacter / enzymology*
  • Enterobacteriaceae Infections / drug therapy*
  • Enterobacteriaceae Infections / microbiology
  • Humans
  • Methazolamide / analogs & derivatives
  • Methazolamide / pharmacology
  • Structure-Activity Relationship
  • Sulfonamides / chemistry*
  • Sulfonamides / pharmacology*

Substances

  • Carbonic Anhydrase Inhibitors
  • Sulfonamides
  • benzenesulfonamide
  • Carbonic Anhydrase I
  • Acetazolamide
  • Methazolamide