Toxicology Research Group of Southern Scientific Centre of Russian Academy of Science, 41 Chekhova Str., 344006 Rostov-on-Don, Russia.
Department of Chemistry, Lomonosov Moscow State University, Leninskie gory 1-3, 119991 Moscow, Russia.
Molecules. 2022 Jun 20;27(12):3961. doi: 10.3390/molecules27123961.
Natural or synthetic antioxidants with biomimetic fragments protect the functional and structural integrity of biological molecules at a minimum concentration, and may be used as potential chemotherapeutic agents. This paper is devoted to in silico and in vitro evaluation of the antioxidant and cytotoxic properties of synthetic analogues of natural compounds-aromatic oligosulfides. The antiradical and SOD-protective activity of oligosulfides was demonstrated in the reaction with O generated in enzymatic and non-enzymatic systems. It was found that phenol-containing disulfides significantly reduced the accumulation level of hydroperoxides and secondary carbonyl thiobarbituric acid reactive substances, which are primary products of oleic acid peroxidation. The antioxidant efficiency of bis(3,5-di--butyl-4-hydroxyphenyl) disulfide increased over time due to the synergistic action of the 2,6-di--butylphenol fragment and the disulfide linker. The highest cytotoxicity on the A-549 and HCT-116 cell lines was found for bis(3,4-dimethoxyphenyl) disulfide. Significant induction of apoptosis in HCT-116 cells in the presence of bis(3,4-dimethoxyphenyl) disulfide indicates the prospect of its use as an antitumor agent. The significant and moderate dependences revealed between various types of activities of the studied aromatic oligosulfides can be used in the development of a strategy for the synthesis and study of target-oriented compounds with predictable biological activity.
天然或合成的具有仿生片段的抗氧化剂以最小浓度保护生物分子的功能和结构完整性，并且可以用作潜在的化疗剂。本文致力于通过计算机模拟和体外实验评估天然化合物-芳香族寡硫化物的合成类似物的抗氧化和细胞毒性特性。寡硫化物在酶和非酶系统中生成的 O 反应中表现出抗自由基和 SOD 保护活性。结果发现，含酚的二硫化物可显著降低过氧化物和次级碳基硫代巴比妥酸反应性物质（油酸过氧化的主要产物）的积累水平。由于 2,6-二叔丁基苯酚片段和二硫化物连接体的协同作用，双（3,5-二-叔丁基-4-羟基苯基）二硫化物的抗氧化效率随时间增加。双（3,4-二甲氧基苯基）二硫化物对 A-549 和 HCT-116 细胞系的细胞毒性最高。在存在双（3,4-二甲氧基苯基）二硫化物的情况下，HCT-116 细胞中明显诱导细胞凋亡表明其有望用作抗肿瘤剂。研究表明，所研究的芳香族寡硫化物的各种类型的活性之间存在显著和中度的依赖性，这可用于开发具有预测生物活性的靶向化合物的合成和研究策略。
