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.

Garlicnin B1, an Active Cyclic Sulfide from Garlic, Exhibits Potent Anti-Inflammatory and Anti-Tumor Activities

“…Our results are consistent with previous literatures, suggesting direct tumoricidal activity of garlicnin B1. Moreover, Osipova et al reported that aromatic oligosulfides induce apoptosis of cancer cells [ 43 ]. In future studies, we will investigate the possible mechanisms of the tumoricidal activity of garlicnin B1, focusing on apoptosis as well as other forms of cell death, such as ferroptosis and autophagy.…”

Diphenyl disulfide potentiates the apoptosis of breast cancer cells through Bax proteolytic activation with accompanying autophagy

“…21,22 Diphenyl disulfide has two phenyl groups that are connected with a disulfide bond. 13 DPDS derivatives, such as bis[2-(acylamino)phenyl] disulfide, 1,2-bis(4-chlorophenyl) disulfide, 1,2-bis (4-methoxyphenyl) disulfide and 1,2-bis(4-nitrophenyl) disulfide, have been shown to have anticancer effects. 18,23 Although DPDS derivatives are reported to inhibit the proliferation of cancers, a recent study also showed that simple DPDS did not significantly affect the proliferation of cancer cells.…”

“…DPDS has strong potential for cytotoxic action against breast cancer cells. Compared to other selected drugs, it showed the highest antioxidant activity against breast adenocarcinoma (MCF‐7) under conditions of adrenaline autoxidation (56% inhibition) and prolonged pro‐oxidant activity, 12 suggesting anticancer activity 13 . The disulfide bond acts as a connector to generate a bifunctional anticancer drug, as with conjugating antibodies and chemotherapy drugs, to enable the specific release of chemotherapy drugs, to reduce off‐target effects and to increase efficiency 14,15 .…”

“…Compared to other selected drugs, it showed the highest antioxidant activity against breast adenocarcinoma (MCF-7) under conditions of adrenaline autoxidation (56% inhibition) and prolonged pro-oxidant activity, 12 suggesting anticancer activity. 13 The disulfide bond acts as a connector to generate a bifunctional anticancer drug, as with conjugating antibodies and chemotherapy drugs, to enable the specific release of chemotherapy drugs, to reduce off-target effects and to increase efficiency. 14,15 Moreover, the disulfide bond conjugated with simple organic groups and similar structures of diallyl disulfide, ajoene and bis [2-(acylamino) phenyl] disulfide has antitumor effects.…”

Anti-Inflammatory Activity of Soluble Epoxide Hydrolase Inhibitors Based on Selenoureas Bearing an Adamantane Moiety

“…The antiradical activity of compounds 4a-g and 5a in the reaction of nonenzymatic quinoid oxidation of adrenaline (1-(3,4-dioxyphenyl)-2-methylaminoethanol) in alkaline bicarbonate buffer was evaluated. As a result of this reaction, not only the superoxide anion radical is formed, but also radicals of carbonate-bicarbonate anions, which makes it possible to reveal the total antiradical activity of potential antioxidants [30,31]. The value of adrenaline autoxidation without the addition of compounds 4a-g and 5a was taken as 100%, the calculated % inhibition indicating the antiradical activity of the derivatives.…”