Efficacy of phosphonium amphiphilic salts against Acanthamoeba genotype T4

Abstract

Acanthamoebae are opportunistic pathogens causing serious human infections, including granulomatous amoebic encephalitis (GAE) and Acanthamoeba keratitis (AK). The treatment of those infections is limited and difficult to date. Recent research demonstrated high antimicrobial activity of phosphonium amphiphilic salts. In the present work we aimed to investigate the anti-Acanthamoeba effect of a series of 16 phosphonium salts. The structure of these synthesized cationic amphiphiles was modified in both the polar and nonpolar parts of the surfactant molecule. The compounds have different alkyl chain lengths (C12 - C18) and different numbers of methyl and phenyl groups (0 - 3) attached to the quaternary phosphorus atom. The following basic physicochemical properties of the compounds were determined: critical micelle concentration (cmc), the surface tension value at the cmc and the surface area per surfactant head group. The cmc values, which express the degree of lipophilicity of compounds, were correlated with biological activities. The effects of phosphonium salts on trophozoites of Acanthamoeba quina and Acanthamoeba hatchetti (both strains of genotype T4) and human erythrocytes were studied. The highest trophocidal activity was recorded for the compound C₁₆P(Me)₂PhBr with the minimal trophocidal concentration (MTC) of 7.8 μM for the A. quina strain and 15.6 μM for the A. hatchetti strain, after 24 h. Its activity was comparable or higher than the activity of drugs currently used in the treatment of Acanthamoeba keratitis. Therefore, this compound is a promising candidate in the fight against infections caused by Acanthamoeba.