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

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.

Graphical abstractCompounds are described that inhibit and disperse MRSA biofilms, with the most potent compound displaying an IC50 of 4.14 μM. 2-Aminoimidazoles also suppress the MIC of oxacillin upwards of 4-fold against MRSA.Figure optionsDownload full-size imageDownload as PowerPoint slideHighlights► Development of a synthetic route to 1,4-substituted 2-aminoimidazoles. ► Lead compounds inhibit both MRSA and multi-drug resistant Acinetobacter baumannii biofilm formation. ► Lead compounds disperse MRSA biofilm formation. ► Lead compound suppresses the oxacillin MIC against MRSA 4-fold.