Abstract

Quinone derivatives of triphenylphosphonium have proven themselves to be effective geroprotectors and antioxidants that prevent oxidation of cell components with participation of active free radicals – peroxide (RO₂·), alkoxy (RO·), and alkyl (R·) radicals, as well as reactive oxygen species (superoxide anion, singlet oxygen). Their most studied representatives are derivatives of plastoquinone (SkQ1) and ubiquinone (MitoQ), which in addition to antioxidant properties also have a strong antibacterial effect. In this study, we investigated antibacterial properties of other quinone derivatives based on decyltriphenylphosphonium (SkQ3, SkQT, and SkQThy). We have shown that they, just like SkQ1, inhibit growth of various Gram-positive bacteria at micromolar concentrations, while being less effective against Gram-negative bacteria, which is associated with recognition of the triphenylphosphonium derivatives by the main multidrug resistance (MDR) pump of Gram-negative bacteria, AcrAB-TolC. Antibacterial action of SkQ1 itself was found to be dependent on the number of bacterial cells. It is important to note that the cytotoxic effect of SkQ1 on mammalian cells was observed at higher concentrations than the antibacterial action, which can be explained by (i) the presence of a large number of membrane organelles, (ii) lower membrane potential, (iii) spatial separation of the processes of energy generation and transport, and (iv) differences in the composition of MDR pumps. Differences in the cytotoxic effects on different types of eukaryotic cells may be associated with the degree of membrane organelle development, energy status of the cell, and level of the MDR pump expression.

中文翻译：

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三苯基鏻与各种醌衍生物的结合物的细胞毒性和抗菌作用的关系

摘要

三苯基鏻的醌衍生物已被证明是有效的老年保护剂和抗氧化剂，可防止细胞成分在活性自由基（过氧化物 (RO ₂ ·)、烷氧基 (RO·) 和烷基 (R·) 自由基）的参与下氧化，以及活性氧（超氧阴离子、单线态氧）。他们研究最多的代表是质体醌（SkQ1）和泛醌（MitoQ）的衍生物，它们除了具有抗氧化特性外，还具有很强的抗菌作用。在本研究中，我们研究了基于癸基三苯基鏻的其他醌衍生物（SkQ3、SkQT 和 SkQThy）的抗菌特性。我们已经证明，它们与 SkQ1 一样，可以在微摩尔浓度下抑制各种革兰氏阳性菌的生长，而对革兰氏阴性菌的效果较差，这与主要的多药耐药性 (MDR) 泵对三苯基鏻衍生物的识别有关革兰氏阴性菌，AcrAB-TolC。研究发现 SkQ1 本身的抗菌作用取决于细菌细胞的数量。值得注意的是，SkQ1 对哺乳动物细胞的细胞毒性作用在比抗菌作用更高的浓度下观察到，这可以通过 (i) 存在大量膜细胞器，(ii) 较低的膜电位，( iii) 能量产生和运输过程的空间分离，以及 (iv) MDR 泵的组成差异。对不同类型真核细胞的细胞毒性作用的差异可能与膜细胞器发育程度、细胞能量状态和MDR泵表达水平有关。