Important Role of Triphenylamine in Modulating the Antibacterial Performance Relationships of Antimicrobial Peptide Mimics by Alkyl Chain Engineering

Multidrug resistance (MDR) bacteria pose a serious threat to human health, and the development of effective antimicrobial drugs is urgent. Herein, we used alkyl chain engineering to design and synthesize two series of antimicrobial peptide mimics with distinct cores: triphenylamine quaternary ammonium derivatives (TPQs) and diphenylethene quaternary ammonium derivatives (BPQs), and we investigated the effect of varying the alkyl chain lengths on antibacterial activity. We found that the introduction of a triphenylamine group significantly enhances the antibacterial activity of short-chain dimethyl quaternary ammonium derivatives while maintaining their excellent biocompatibility. Most notably, TPQ-1 exhibited negligible invasiveness toward living cells and possesses good antimicrobial activities, with good efficacy against biofilms and persisters. Moreover, TPQ-1 exhibited good antimicrobial effects <i>in vivo</i> and significantly accelerated the healing process of methicillin-resistant <i>Staphylococcus aureus</i>-infected wounds. This work promotes the practical application of antimicrobial peptide mimics and triphenylamine derivatives.