Antioxidant Activity and Cytotoxicity of Aromatic Oligosulfides

Abstract

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 O2–• 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-tert-butyl-4-hydroxyphenyl) disulfide increased over time due to the synergistic action of the 2,6-di-tert-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.

Keywords

• aromatic oligosulfides
• antioxidant
• radical scavenging activity
• metal chelating
• cis-9-octadecenoic (oleic) acid
• liver of Russian sturgeon