Identification and characterization of an anti-pseudomonal dichlorocarbazol derivative displaying anti-biofilm activity

Bioorg Med Chem Lett. 2014 Dec 1;24(23):5404-8. doi: 10.1016/j.bmcl.2014.10.039.

Abstract

Pseudomonas aeruginosa strains resistant towards all currently available antibiotics are increasingly encountered, raising the need for new anti-pseudomonal drugs. We therefore conducted a medium-throughput screen of a small-molecule collection resulting in the identification of the N-alkylated 3,6-dihalogenocarbazol 1-(sec-butylamino)-3-(3,6-dichloro-9H-carbazol-9-yl)propan-2-ol (MIC = 18.5 μg mL⁻¹). This compound, compound 1, is bacteriostatic towards a broad spectrum of Gram-positive and Gram-negative pathogens, including P. aeruginosa. Importantly, 1 also eradicates mature biofilms of P. aeruginosa. 1 displays no cytotoxicity against various human cell types, pointing to its potential for further development as a novel antibacterial drug.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anti-Bacterial Agents / therapeutic use*
  • Biofilms
  • Carbazoles / analysis
  • Carbazoles / chemistry*
  • Humans
  • Microbial Sensitivity Tests
  • Pseudomonas aeruginosa / isolation & purification*

Substances

  • Anti-Bacterial Agents
  • Carbazoles