Citral derived amides as potent bacterial NorA efflux pump inhibitors

Bioorg Med Chem. 2008 Jul 1;16(13):6535-43. doi: 10.1016/j.bmc.2008.05.030. Epub 2008 May 17.

Abstract

Monoterpene citral and citronellal have been used as starting material for the preparation of 5,9-dimethyl-deca-2,4,8-trienoic acid amides and 9-formyl-5-methyl-deca-2,4,8-trienoic acid amides. The amides on bioevaluation as efflux pump inhibitors (EPIs) against Staphylococcus aureus 1199 and NorA overexpressing S. aureus 1199B bacteria resulted in the identification of several of these as potent EPIs. Many of these amides have been shown to possess potency higher or equivalent to known EPIs such as reserpine, verapamil, carsonic acid, and piperine. In this communication, we report a convenient synthesis of alkenyl amides, their bioevaluation and identification as efflux pump inhibitors against S. aureus.

MeSH terms

  • Amides / chemical synthesis*
  • Amides / chemistry
  • Amides / pharmacology*
  • Bacterial Proteins / antagonists & inhibitors*
  • Bacterial Proteins / metabolism*
  • Ciprofloxacin / chemistry
  • Ciprofloxacin / pharmacology
  • Molecular Structure
  • Multidrug Resistance-Associated Proteins / antagonists & inhibitors*
  • Multidrug Resistance-Associated Proteins / metabolism*
  • Staphylococcus aureus / drug effects
  • Structure-Activity Relationship

Substances

  • Amides
  • Bacterial Proteins
  • Multidrug Resistance-Associated Proteins
  • NorA protein, Staphylococcus
  • Ciprofloxacin