Design and Synthesis of New Antibacterial Ammonium Amphiphiles Based on Natural Products

The development of new antimicrobial agents remains critical to combating the increasing pathogen resistance. In this study, a series of amphiphilic derivatives that combine the properties of quaternary ammonium salts and antibacterial peptide mimics was designed and synthesized based on bromotyrosine alkaloids. All compounds demonstrated good antibacterial activity against S. aureus , E. coli , and P. aeruginosa strains except that of оxacillin‐resistant P. aeruginosa . Ammonium amphiphiles 9 and 11 with a dodecyl chain and a three‐ or four‐carbon linker showed the most potent antibacterial activity against S. aureus and E. coli , including colistin‐resistant strains, and P. aeruginosa PA01 with MIC values ranging from 2 to 4 μg/mL. Notably, 9 and 11 also inhibited biofilm formation by the standard strains of S. aureus , E. coli , P. aeruginosa , and colistin‐resistant E. coli by 100%.