Synthesis of sulfonamides with effective inhibitory action against Porphyromonas gingivalis γ-carbonic anhydrase

Bioorg Med Chem Lett. 2014 Aug 15;24(16):4006-10. doi: 10.1016/j.bmcl.2014.06.024. Epub 2014 Jun 18.

Abstract

New benzenesulfonamides incorporating GABA or N-α-acetyl-L-lysine scaffolds as well as guanidine functionalities as water solubilizing moieties were obtained, using 4-aminoethyl/methyl-benzenesulfonamide and metanilamide/sulfanilamide as zinc-binding motives. The new compounds were medium potency inhibitors of the widespread cytosolic human carbonic anhydrase (CA, EC 4.2.1.1) isoforms I and II and more effective inhibitors (KIs low nanomolar range) of the bacterial γ-CA from the oral pathogen Porphyromonas gingivalis. These sulfonamides may be useful tools for understanding the physiological role of bacterial CAs in pathogenesis of some infectious disease.

Keywords: Amino acid; Carbonic anhydrase; Enzyme inhibitor; Porphyromonas gingivalis; Sulfonamide.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Carbonic Anhydrase Inhibitors / chemical synthesis
  • 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 / chemical synthesis
  • Sulfonamides / chemistry
  • Sulfonamides / pharmacology*

Substances

  • Carbonic Anhydrase Inhibitors
  • Sulfonamides
  • Carbonic Anhydrases