Benzylaminoethylureido-Tailed Benzenesulfonamides Show Potent Inhibitory Activity against Bacterial Carbonic Anhydrases

ChemMedChem. 2020 Dec 15;15(24):2444-2447. doi: 10.1002/cmdc.202000680. Epub 2020 Oct 28.

Abstract

A series of benzylaminoethylureido-tailed benzenesulfonamides was analyzed for their inhibition potential against bacterial carbonic anhydrases (CAs) such as VhCA α, β, and γ from Vibrio cholerae, and BpsCA β and γ-CAs from Burkholderia pseudomallei. Growing drug resistance against antibiotics demands alternative targets and mechanisms of action. As CA is essential for the survival of bacteria, such enzymes have the potential for developing new antibiotics. Most of the compounds presented excellent inhibition potential against VhCA γ compared to α and β, with Ki values in the range of 82.5-191.4 nM. Several sulfonamides exhibited excellent inhibition against BpsCA β with Ki values in the range of 394-742.8 nM. Recently it has been demonstrated that sufonamide CA inhibitors are effective against vancomycin-resistant enterococci. These data show that CA inhibition of pathogenic bacteria may lead to a new class of antibiotics.

Keywords: B. pseudomallei; V. cholera; antibiotics; benzenesulfonamides; carbonic anhydrases.

MeSH terms

  • Anti-Bacterial Agents / chemical synthesis
  • Anti-Bacterial Agents / pharmacology*
  • Bacterial Proteins / antagonists & inhibitors*
  • Burkholderia pseudomallei / enzymology
  • Carbonic Anhydrase Inhibitors / chemical synthesis
  • Carbonic Anhydrase Inhibitors / pharmacology*
  • Microbial Sensitivity Tests
  • Molecular Structure
  • Structure-Activity Relationship
  • Sulfonamides / chemical synthesis
  • Sulfonamides / pharmacology*
  • Vibrio cholerae / enzymology

Substances

  • Anti-Bacterial Agents
  • Bacterial Proteins
  • Carbonic Anhydrase Inhibitors
  • Sulfonamides