Pyrazolo[4,3-c][1,2]benzothiazines 5,5-dioxide: a promising new class of Staphylococcus aureus NorA efflux pump inhibitors

J Med Chem. 2012 Apr 12;55(7):3568-72. doi: 10.1021/jm201446h. Epub 2012 Apr 3.

Abstract

The increasing resistance to antibacterials commonly employed in the clinic and the growth of multidrug resistant strains suggest that the development of new therapeutic approaches should be of primary concern. In this context, EPIs may restore life to old drugs. In the present work, the EPI activity of the COX-2 inhibitor celecoxib was confirmed and a new class of pyrazolo[4,3-c][1,2]benzothiazine 5,5-dioxide analogues acting as inhibitors of the Staphylococcus aureus NorA multidrug efflux pump was identified.

MeSH terms

  • Anti-Bacterial Agents / chemical synthesis*
  • Anti-Bacterial Agents / chemistry
  • Anti-Bacterial Agents / pharmacology
  • Bacterial Proteins / antagonists & inhibitors*
  • Celecoxib
  • Cyclooxygenase 2 Inhibitors / chemistry
  • Cyclooxygenase 2 Inhibitors / pharmacology
  • Drug Resistance, Multiple, Bacterial
  • Drug Synergism
  • Microbial Sensitivity Tests
  • Models, Molecular
  • Multidrug Resistance-Associated Proteins / antagonists & inhibitors*
  • Pyrazoles / chemical synthesis*
  • Pyrazoles / chemistry
  • Pyrazoles / pharmacology
  • Small Molecule Libraries
  • Staphylococcus aureus / drug effects
  • Staphylococcus aureus / metabolism*
  • Structure-Activity Relationship
  • Sulfonamides / chemistry
  • Sulfonamides / pharmacology
  • Thiazines / chemical synthesis*
  • Thiazines / chemistry
  • Thiazines / pharmacology

Substances

  • Anti-Bacterial Agents
  • Bacterial Proteins
  • Cyclooxygenase 2 Inhibitors
  • Multidrug Resistance-Associated Proteins
  • Pyrazoles
  • Small Molecule Libraries
  • Sulfonamides
  • Thiazines
  • NorA protein, Staphylococcus
  • Celecoxib