Conformationally-restricted analogues of efflux pump inhibitors that potentiate the activity of levofloxacin in Pseudomonas aeruginosa

Bioorg Med Chem Lett. 2003 Aug 18;13(16):2755-8. doi: 10.1016/s0960-894x(03)00556-0.

Abstract

Conformational restriction of the ornithine residue of the efflux pump inhibitor D-ornithine-D-homophenylalanine-3-aminoquinoline (MC-02,595, 2) furnished bioisosteric proline derivatives that were less toxic in vivo and as active as the lead in potentiating the activity of the fluoroquinolone levofloxacin via the inhibition of efflux pumps in Pseudomonas aeruginosa.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aminobutyrates / chemistry
  • Aminoquinolines / chemical synthesis*
  • Aminoquinolines / pharmacology
  • Aminoquinolines / toxicity
  • Animals
  • Anti-Infective Agents / chemical synthesis*
  • Anti-Infective Agents / pharmacology*
  • Anti-Infective Agents / toxicity
  • Bacterial Outer Membrane Proteins / antagonists & inhibitors*
  • Drug Synergism
  • Lethal Dose 50
  • Levofloxacin*
  • Membrane Transport Modulators*
  • Membrane Transport Proteins / antagonists & inhibitors*
  • Mice
  • Ofloxacin / pharmacology*
  • Ornithine / chemistry
  • Pseudomonas aeruginosa / drug effects
  • Structure-Activity Relationship

Substances

  • Aminobutyrates
  • Aminoquinolines
  • Anti-Infective Agents
  • Bacterial Outer Membrane Proteins
  • Membrane Transport Modulators
  • Membrane Transport Proteins
  • Levofloxacin
  • 2-amino-4-phenylbutyric acid
  • Ofloxacin
  • Ornithine