A flexible approach to 1,4-di-substituted 2-aminoimidazoles that inhibit and disperse biofilms and potentiate the effects of β-lactams against multi-drug resistant bacteria

Eur J Med Chem. 2013 Apr:62:59-70. doi: 10.1016/j.ejmech.2012.12.005. Epub 2012 Dec 20.

Abstract

The pyrrole-imidazole alkaloids are a 2-aminoimidazoles containing family of natural products that possess anti-biofilm activity. A library of 1,4-di-substituted 2-aminoimidazole/triazoles (2-AITs) was synthesized, and its anti-biofilm activity as well as oxacillin resensitization efficacy toward methicillin resistant Staphylococcus aureus (MRSA) was investigated. These 2-AITs were found to inhibit biofilm formation by MRSA with low micromolar IC50 values. Additionally, the most active compound acted synergistically with oxacillin against MRSA lowering the minimum inhibitory concentration (MIC) 4-fold.

Publication types

  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Biofilms / drug effects*
  • Dose-Response Relationship, Drug
  • Imidazoles / chemical synthesis
  • Imidazoles / chemistry
  • Imidazoles / pharmacology*
  • Methicillin-Resistant Staphylococcus aureus / drug effects*
  • Molecular Structure
  • Structure-Activity Relationship
  • beta-Lactams / chemistry
  • beta-Lactams / pharmacology*

Substances

  • Imidazoles
  • beta-Lactams
  • 2-aminoimidazole