Monocatenary histidine-based surfactants: Role of the alkyl chain length in antimicrobial activity and their selectivity over red blood cells

Abstract

Due to the rapid worldwide emergence of resistant bacteria the development of new antimicrobial compounds with different modes of action is of tremendous importance in biomedicinal chemistry. Here we report for the first time the synthesis of monocatenary cationic histidine-based surfactants of different alkyl chain length. The polar head of these surfactants consists of the histidine amino-acid with methylene groups at N(π) and N(τ)-positions on the imidazole group of histidine. Given their simple chemical structure these new surfactants can be prepared using a straightforward and economical procedure. Tensiometry and conductimetry were used to study the self-aggregation of these molecules, whose number of positive charges is pH-dependent. These compounds showed remarkable growth inhibition activity against several Gram-positive and Gram-negative bacteria as well as fungus. The antimicrobial activity of these surfactants was influenced by the alkyl chain length, the most active compound being C14 homologous. The hemolytic activity was found to increase with the lengthening of the alkyl chain. Encouragingly, the antimicrobial activity of these new surfactants against Gram-positive bacteria occurred at lower concentrations than their erythrocyte toxicity. The relationship between structure, physicochemical properties and biological activity of the synthesized compounds is discussed. The results show that histidine-based-surfactants are excellent candidates for the development of novel antimicrobial agents with potential applications in biomedicine.