RELATIONSHIP OF CYTOTOXIC AND ANTIMICROBIAL EFFECTS OF TRIPHENYLPHOSPHONIUM CONJUGATES WITH VARIOUS QUINONE DERIVATIVES

Abstract

Quinone derivatives of triphenylphosphonium have proven themselves to be effective geroprotectors and antioxidants that prevent the oxidation of cell components with the participation of active free radicals – peroxide (RO2•), alkoxy (RO•), alkyl (R•), as well as reactive oxygen species (superoxide anion, singlet oxygen). The most studied representatives are derivatives of plastoquinone (SkQ1) and ubiquinone (MitoQ), which in addition to antioxidant properties also had a strong antibacterial effect. Other quinone derivatives based on decyltriphenylphosphonium (SkQ3, SkQT, and SkQThy) have been less studied and their antibacterial activity remains undiscovered. In this work, we investigated the antibacterial properties of quinone derivatives based on decyltriphenylphosphonium. We have shown that, as in the case of SkQ1, they are effective against various gram-positive bacteria, while they are not so effective against gram-negative bacteria. This is associated with their recognition by the main multidrug resistance pump of gram-negative bacteria AcrAB-TolC. Moreover, in the case of SkQ1 itself, there is a dependence of its action on the number of bacterial cells and the molar amount of the antibiotic itself, which distinguishes it from conventional antibiotics. At the same time, the cytotoxic effect on mammalian cells is observed in higher concentrations, which suggests the presence of a protective effect caused by the separation of the process of energy generation and transport on the cell membrane. Another possible explanation could be the different composition of multidrug-resistant (MDR) pumps. The difference in cytotoxic effects on mammalian cells may be due to different expression profiles of MDR pumps in different cell types.