Sulfonamide inhibition studies of the γ-carbonic anhydrase from the oral pathogen Porphyromonas gingivalis

Bioorg Med Chem Lett. 2014 Jan 1;24(1):240-4. doi: 10.1016/j.bmcl.2013.11.030. Epub 2013 Nov 21.

Abstract

A carbonic anhydrase (CA, EC 4.2.1.1) denominated PgiCA, belonging to the γ-class, from the oral pathogenic bacteria Porphyromonas gingivalis, the main causative agent of periodontitis, was investigated for its inhibition profile with sulfonamides and one sulfamate. Dichlorophenamide, topiramate and many simple aromatic/heterocyclic sulfonamides were ineffective as PgiCA inhibitors whereas the best inhibition was observed with halogenosulfanilamides incorporating heavy halogens, 4-hydroxy- and 4-hydroxyalkyl-benzenesulfonamides, acetazolamide, methazolamide, zonisamide, indisulam, celecoxib, saccharin and hydrochlorothiazide (KIs in the range of 131-380nM). The inhibition profile of PgiCA was very different from that of CAM, hCA I and II or the β-CA from a protozoan parasite (Leishmania donovani chagasii). Identification of potent and possibly selective inhibitors of PgiCA may lead to pharmacological tools useful for understanding the physiological role(s) of this enzyme.

Keywords: Carbonic anhydrase; Gamma-class enzyme; Porphyromonas gingivalis; Sulfonamide.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Carbonic Anhydrase Inhibitors / chemistry
  • Carbonic Anhydrase Inhibitors / pharmacology*
  • Carbonic Anhydrases / metabolism*
  • Dose-Response Relationship, Drug
  • Humans
  • Molecular Structure
  • Porphyromonas gingivalis / enzymology*
  • Structure-Activity Relationship
  • Sulfonamides / chemistry
  • Sulfonamides / pharmacology*

Substances

  • Carbonic Anhydrase Inhibitors
  • Sulfonamides
  • Carbonic Anhydrases