Development of potent inhibitors of pyocyanin production in Pseudomonas aeruginosa

J Med Chem. 2015 Feb 12;58(3):1298-306. doi: 10.1021/jm5015082. Epub 2015 Feb 3.

Abstract

The development of new approaches for the treatment of antimicrobial-resistant infections is an urgent public health priority. The Pseudomonas aeruginosa pathogen, in particular, is a leading source of infection in hospital settings, with few available treatment options. In the context of an effort to develop antivirulence strategies to combat bacterial infection, we identified a series of highly effective small molecules that inhibit the production of pyocyanin, a redox-active virulence factor produced by P. aeruginosa. Interestingly, these new antagonists appear to suppress P. aeruginosa virulence factor production through a pathway that is independent of LasR and RhlR.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Amides / chemical synthesis
  • Amides / chemistry
  • Amides / pharmacology*
  • Anti-Bacterial Agents / chemical synthesis
  • Anti-Bacterial Agents / chemistry
  • Anti-Bacterial Agents / pharmacology*
  • Dose-Response Relationship, Drug
  • Microbial Sensitivity Tests
  • Molecular Structure
  • Pseudomonas aeruginosa / chemistry
  • Pseudomonas aeruginosa / drug effects*
  • Pseudomonas aeruginosa / metabolism*
  • Pyocyanine / biosynthesis*
  • Pyocyanine / chemistry
  • Pyridines / chemical synthesis
  • Pyridines / chemistry
  • Pyridines / pharmacology*
  • Small Molecule Libraries / chemical synthesis
  • Small Molecule Libraries / chemistry
  • Small Molecule Libraries / pharmacology*
  • Structure-Activity Relationship

Substances

  • Amides
  • Anti-Bacterial Agents
  • Pyridines
  • Small Molecule Libraries
  • Pyocyanine