Cationic Surfactants Based on Arginine-Phenylalanine and Arginine-Tryptophan: Synthesis, Aggregation Behavior, Antimicrobial Activity, and Biodegradation.

Abstract

Cationic surfactants have great potential as drug vehicles and for use in gene therapy (cationic vesicles made from cationic surfactants can encapsulate RNA or DNA for cellular transfer). They can also be used as antimicrobial and antifungal agents to treat human infections. In an era of increasing antimicrobial resistance, the development of new biocompatible surfactants suitable for application as antimicrobial agents is of high interest. In this work, a library of amino acid-based surfactants was synthesized, characterized and tested for antimicrobial activity. The head group architecture (number and type of amino acids, density of cationic charge, ionic character) and the hydrophobic moiety (alkyl chain length and position of the hydrophobic group) were systematically modified, and the effect on the surfactant biological and aggregation behavior was studied. Thus, the pKa values, micellization process, antimicrobial efficiency and biodegradability were evaluated. The critical micelle concentration values of the surfactants depended on their hydrophobic character, but changes in the polar head as well as the position and length of the alkyl chain also significantly affected activity against some of the tested microorganisms. Moreover, biodegradability was closely related to the hydrophobic character of the surfactant and attachment of the alkyl chain to the polar head. The structure-activity relationships established here may open perspectives for the design of effective biodegradable antimicrobial materials that can overcome emerging resistance.