Department of Chemistry, Astrakhan State Technical University, 16 Tatisheva str., Astrakhan 414056, Russia; Toxicology Research Group of Southern Scientific Centre of Russian Academy of Science, 41 Chekhova str., Rostov-on-Don 344006, Russia.
Department of Chemistry, Astrakhan State Technical University, 16 Tatisheva str., Astrakhan 414056, Russia.
Bioorg Chem. 2019 Aug;89:103003. doi: 10.1016/j.bioorg.2019.103003. Epub 2019 May 20.
A number of asymmetrical thioethers based on 3,5-di-tert-butylcatechol containing sulfur atom bonding with physiologically active groups in the sixth position of aromatic ring have been synthesized and the electrochemical properties, antioxidant, cryoprotective activities of new thioethers have been evaluated. Cyclic voltammetry was used to estimate the oxidation potentials of thioethers in acetonitrile. The electrooxidation of compounds at the first stage leads to the formation of o-benzoquinones. The antioxidant activities of the compounds were determined using 2,2'-diphenyl-1-picrylhydrazyl radical (DPPH) assay, experiments on the oxidative damage of the DNA, the reaction of 2,2'-azobis(2-amidinopropane hydrochloride) (AAPH) induced glutathione depletion (GSH), the process of lipid peroxidation of rat liver (Wistar) homogenates in vitro, and iron(II) chelation test. Compounds 1-9 have greater antioxidant effectiveness than 3,5-di-tert-butylcatechol (CatH) in all assays. The variation of physiologically active groups at sulfur atom allows to regulate lipophilic properties and antioxidant activity of compounds. Thioethers 3, 4 and 7 demonstrate the combination of radical scavenging, antioxidant activity and iron(II) binding properties. The researched compounds 1-9 were studied as possible cryoprotectants of the media for cryopreservation of the Russian sturgeon sperm. Novel cryoprotective additives in cryomedium reduce significantly the content of membrane-permeating agent (DMSO). A cryoprotective effect of an addition of the catechol thioethers depends on the structure of groups at sulfur atom. The cryoprotective properties of compounds 3, 4 and 7 are caused by combination of catechol fragment, bonded by a thioether linker with a long hydrocarbon chain and a terminal ionizable group or with a biologically relevant acetylcysteine residue.
已合成了一系列基于 3,5-二叔丁基邻苯二酚的不对称硫醚，其中硫原子与芳环第六位的生理活性基团键合，并评估了新硫醚的电化学性质、抗氧化和抗冷冻保护活性。循环伏安法用于估算硫醚在乙腈中的氧化电位。化合物在第一阶段的电氧化导致邻苯醌的形成。采用 2,2'-二苯基-1-苦基肼基自由基（DPPH）测定法、DNA 氧化损伤实验、2,2'-偶氮双（2-脒基丙烷）盐酸盐（AAPH）诱导谷胱甘肽耗竭（GSH）反应、大鼠肝（Wistar）匀浆体外脂质过氧化过程和铁（II）螯合试验来测定化合物的抗氧化活性。在所有测定中，化合物 1-9 的抗氧化效果均大于 3,5-二叔丁基邻苯二酚（CatH）。硫原子上生理活性基团的变化可调节化合物的亲脂性和抗氧化活性。硫醚 3、4 和 7 表现出自由基清除、抗氧化活性和铁（II）结合特性的结合。研究的化合物 1-9 被研究为俄罗斯鲟精子低温保存中冷冻保护剂的候选物。新型冷冻保护添加剂在冷冻培养基中可显著降低膜透性剂（DMSO）的含量。添加儿茶酚硫醚的冷冻保护作用取决于硫原子上基团的结构。化合物 3、4 和 7 的冷冻保护性质是由通过硫醚键合与长烃链和末端可电离基团结合的儿茶酚片段或与生物相关的乙酰半胱氨酸残基结合的儿茶酚片段引起的。
