Bacterial infections and antibiotic resistance present an ever-increasing threat to human health worldwide, and medicine urgently needs new alternatives for the successful treatment of bacterial infections. Cationic surfactants have proven to be effective antibacterial agents due to their ability to disrupt bacterial membranes, inhibit biofilm formation, and combat a broad spectrum of pathogens. We employed a orthogonal click chemistry strategy for the efficient modular synthesis of six novel cationic surfactants. Our results emphasize the strong correlation between the surfactant design and its antibacterial potential. Among these six cationic surfactants we identified a prime candidate, which possessed an impressive antibacterial effect against gram-positive and gram-negative bacteria, including drug-resistant strains. We found that our surfactant can prevent biofilm formation and eradicate already existing biofilms. Cryo-TEM imaging was used to reveal the membrane-disrupting properties of the surfactant. In-vivo wound healing experiments underline the surfactants’ ability to inhibit wound infections. Cationic surfactants often face the challenge of balancing strong antibacterial activity with minimal cytotoxicity. Our strategic design and orthogonal click chemistry approach have enabled precise fine-tuning of molecular structures to achieve an optimal balance between antibacterial efficacy and biocompatibility, effectively overcoming this critical limitation.
