Work

Green cationic phenylalanine and tryptophan-based surfactants: Influence of the polar head amino acids and hydrophobic character on the self-aggregation, antimicrobial activity, and environmental behavior

Year: 2025

Type: article

Abstract: • Phenylalanine and tryptophan-based surfactants form prolate ellipsoidal micelles at low CMC. • These surfactants exhibit high antifungal activity and efficiently remove the metabolic activity of C. albicans biofilms. • The C 12 and C 14 homologs exhibit good selectivity for Candida strains over mammalian cells. • All phenylalanine-based compounds can be considered readily biodegradable surfactants. • These compounds significantly improve the environmental behavior of classical QACs. Antimicrobial resistance (AR) has become a global threat to public health systems and biofilm development plays a key role in this issue; it is estimated that 80 % of microbial infections in humans are caused by biofilms. So, there is an urgent need to explore efficient broad-spectrum antimicrobial compounds that can prevent and eradicate biofilms. In this work, we propose the use of simple, economical, and low molecular weight amino acid-based surfactants to fight against AR. These compounds consist of one amino acid (phenylalanine or tryptophan) linked through an amide bond to one C 8 –C 14 alkyl chain. Surface tension measurements and SAXS analysis show the formation of prolate ellipsoidal micelles at low critical micelle concentration (CMC around 0.2–11 mM). These compounds exhibit antifungal activity against a broad-spectrum Candida strain, with the C 14 derivatives being the most efficient agents with MIC values of 16–32 µM. They can disrupt mature C. albicans biofilms at very low concentrations, and the long-chain derivatives can easily condense DNA. Interestingly, these surfactants exhibited lower aquatic toxicity and better biodegradability than the widely used quaternary ammonium cationic surfactants (QAC S ). This is an important property given that non-biodegradable compounds lead to persistence in the environment, increasing the proliferation of antimicrobial resistance. The results obtained in this work allow for establishing a structure–activity relationship that can help in designing new biodegradable and biocompatible antimicrobial surfactants. Moreover, given their biological and physicochemical properties, these surfactants can be an interesting alternative to the existing antimicrobials for medical and industrial applications.

Source: Journal of Molecular Liquids

DOI: 10.1016/j.molliq.2025.127620