Novel quaternary ammonium compounds derived from aromatic and cyclic amino acids: Synthesis, physicochemical studies and biological evaluation

Abstract

Novel quaternary ammonium surfactants (QUATs) derived from phenylalaninyl-proline dipeptide with chain length C₁₂ and C₁₄ were synthesised as potential active ingredients to be used in body cleansing formulations. The physicochemical properties and biological activities of the QUATs were determined in both single and in mixed surfactant system with either the conventional anionic surfactant sodium dodecyl sulphate (SDS) or sodium N-dodecyl prolinate. The C₁₂ QUAT derivative showed antagonistic behaviour in both SDS and sodium N-dodecyl prolinate mixed surfactant system. Comparing the mixed system of the C₁₂ QUAT with SDS and sodium N-dodecyl prolinate, it was found that the latter displayed better antibacterial activity together with the lower ocular irritation. The C₁₂ QUAT-sodium N-dodecyl prolinate mixture were non cytotoxic at a concentration corresponding to its MIC value, showing that the mixture was selective towards bacterial cells rather than mammalian cell lines. Diffusion measurements showed that the sodium N-dodecyl prolinate surfactant consisted of 26 molecules per micelle in water but only 3 molecules per micelle in DMSO/water (1:1). On the other hand, C₁₂ QUAT did not form a micelle in DMSO/Water. Membrane permeability studies of the C₁₂ QUAT and sodium N-dodecyl prolinate showed that these surfactants are capable to penetrate into deeper skin layers to exert their antibacterial and cleansing action and hence can be used as a promising candidate as active ingredients in body wash formulations.

Keywords: Antibacterial activity; Cytotoxicity; Dipeptide; Foaming ability; Membrane permeability; Mixed surfactant system; Ocular irritation; Phenylalanine; Proline; Quaternary ammonium surfactants.