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

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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.

About the authors

P. A Nazarov

Belozersky Institute of Physico-Chemical Biology, Lomonosov Moscow State University

Email: nazarovpa@gmail.com
119991 Moscow, Russia

L. A Zinovkina

Faculty of Bioengineering and Bioinformatics, Lomonosov Moscow State University

119991 Moscow, Russia

A. A Brezgunova

Belozersky Institute of Physico-Chemical Biology, Lomonosov Moscow State University; Faculty of Bioengineering and Bioinformatics, Lomonosov Moscow State University

119991 Moscow, Russia; 119991 Moscow, Russia

K. G Lyamzaev

Belozersky Institute of Physico-Chemical Biology, Lomonosov Moscow State University; Russian Gerontological Research and Clinical Center, Federal State Autonomous Educational Institution of Russian National Research Medical University named after N. I. Pirogov Ministry of Health of Russia

119991 Moscow, Russia; 129226 Moscow, Russia

A. V Golovin

Faculty of Bioengineering and Bioinformatics, Lomonosov Moscow State University

119991 Moscow, Russia

M. V Karakozova

Belozersky Institute of Physico-Chemical Biology, Lomonosov Moscow State University

119991 Moscow, Russia

E. A Kotova

Belozersky Institute of Physico-Chemical Biology, Lomonosov Moscow State University

119991 Moscow, Russia

E. Yu Plotnikov

Belozersky Institute of Physico-Chemical Biology, Lomonosov Moscow State University

119991 Moscow, Russia

R. A Zinovkin

Belozersky Institute of Physico-Chemical Biology, Lomonosov Moscow State University; Russian Gerontological Research and Clinical Center, Federal State Autonomous Educational Institution of Russian National Research Medical University named after N. I. Pirogov Ministry of Health of Russia

119991 Moscow, Russia; 129226 Moscow, Russia

M. V Skulachev

Belozersky Institute of Physico-Chemical Biology, Lomonosov Moscow State University; Research Institute of Mitoengineering, Lomonosov Moscow State University

119991 Moscow, Russia; 119991 Moscow, Russia

Yu. N Antonenko

Belozersky Institute of Physico-Chemical Biology, Lomonosov Moscow State University

119991 Moscow, Russia

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