Pharmacophore-Based Repositioning of Approved Drugs as Novel Staphylococcus aureus NorA Efflux Pump Inhibitors

J Med Chem. 2017 Feb 23;60(4):1598-1604. doi: 10.1021/acs.jmedchem.6b01439. Epub 2017 Feb 8.

Abstract

An intriguing opportunity to address antimicrobial resistance is represented by the inhibition of efflux pumps. Focusing on NorA, the most important efflux pump of Staphylococcus aureus, an efflux pump inhibitors (EPIs) library was used for ligand-based pharmacophore modeling studies. By exploitation of the obtained models, an in silico drug repositioning approach allowed for the identification of novel and potent NorA EPIs.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anti-Bacterial Agents / chemistry*
  • Anti-Bacterial Agents / pharmacology*
  • Bacterial Proteins / antagonists & inhibitors*
  • Bacterial Proteins / metabolism
  • Drug Repositioning
  • Humans
  • Ligands
  • Models, Molecular
  • Multidrug Resistance-Associated Proteins / antagonists & inhibitors*
  • Multidrug Resistance-Associated Proteins / metabolism
  • Staphylococcal Infections / drug therapy*
  • Staphylococcus aureus / drug effects*
  • Staphylococcus aureus / metabolism

Substances

  • Anti-Bacterial Agents
  • Bacterial Proteins
  • Ligands
  • Multidrug Resistance-Associated Proteins
  • NorA protein, Staphylococcus