Arginine-Derived Cationic Surfactants Containing Phenylalanine and Tryptophan: Evaluation of Antifungal Activity, Biofilm Eradication, Cytotoxicity, and Ecotoxicity

Due to the growing emergence of bacterial and fungal resistance, there is an urgent need for novel antimicrobial compounds. Cationic surfactants are effective antimicrobial agents; however, traditional quaternary ammonium compounds (QACs) are increasingly scrutinized due to their cytotoxicity, poor biodegradability, and harmful effects on aquatic ecosystems. While the antimicrobial efficacy of many new biocides, including QACs, has been extensively studied, comprehensive experimental strategies that simultaneously assess antimicrobial activity, mammalian cell toxicity, and ecotoxicity remain limited. Recent studies have reported that amino-acid-based surfactants containing arginine-phenylalanine and arginine-tryptophan exhibit excellent antibacterial activity and are biodegradable. This work extends their biological characterization to evaluate their potential applications. Specifically, we examined how variations in the head group architecture and hydrophobic moiety influence antifungal and antibiofilm activity. We also assessed how these structural parameters impact cytotoxicity and ecotoxicity. These compounds demonstrated strong activity against a wide range of Candida strains. Their hydrophobic character primarily influenced both antifungal efficacy and cytotoxicity. Importantly, these surfactants exhibited potent antimicrobial and antibiofilm effects at non-cytotoxic concentrations. Notably, their aquatic toxicity was significantly lower than that of conventional QACs.