Evaluation of 4,5-disubstituted-2-aminoimidazole-triazole conjugates for antibiofilm/antibiotic resensitization activity against MRSA and Acinetobacter baumannii

ChemMedChem. 2011 Dec 9;6(12):2243-51. doi: 10.1002/cmdc.201100316. Epub 2011 Sep 16.

Abstract

A library of 4,5-disubstituted-2-aminoimidazole-triazole conjugates (2-AITs) was synthesized, and the antibiofilm activity was investigated. This class of small molecules was found to inhibit biofilm formation by methicillin-resistant Staphylococcus aureus (MRSA) at low-micromolar concentrations; 4,5-disubstituted-2-AITs were also able to inhibit and disperse Acinetobacter baumannii biofilms. The activities of the lead compounds were compared against the naturally occurring biofilm dispersant cis-2-decenoic acid and were revealed to be more potent. The ability of selected compounds to resensitize MRSA to traditional antibiotics (resensitization activity) was also determined. Lead compounds were observed to resensitize MRSA to oxacillin by 2-4-fold.

Publication types

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

MeSH terms

  • Acinetobacter baumannii / drug effects*
  • Acinetobacter baumannii / physiology
  • Anti-Bacterial Agents / chemical synthesis
  • Anti-Bacterial Agents / chemistry
  • Anti-Bacterial Agents / pharmacology*
  • Biofilms / drug effects*
  • Imidazoles / chemistry*
  • Methicillin-Resistant Staphylococcus aureus / drug effects*
  • Methicillin-Resistant Staphylococcus aureus / physiology
  • Oxacillin / chemistry
  • Oxacillin / pharmacology
  • Structure-Activity Relationship
  • Triazoles / chemistry*

Substances

  • Anti-Bacterial Agents
  • Imidazoles
  • Triazoles
  • 2-aminoimidazole
  • Oxacillin