Antioxidant Activity of New Sulphur- and Selenium-Containing Analogues of Potassium Phenosan against H2O2-Induced Cytotoxicity in Tumour Cells.

Among known phenolic antioxidants, the overwhelming majority of compounds have lipophilic properties and the number of known water-soluble compounds is very small. The list of hydrophilic phenolic antioxidants can be expanded via the synthesis of a structurally related series of polyfunctional compounds for further research on their biological activity in vitro. New sulphur- and selenium-containing analogues of antioxidant potassium phenosan were synthesised. In vitro cytotoxicity and cytostaticity as well as antioxidant activity against H2O2-induced cytotoxicity to human cell lines (HepG2, Hep-2 and MCF-7) were investigated by high-content analysis. A selenium-containing analogue showed higher biological activity than did a sulphur-containing one. As compared to the activity of potassium phenosan, the selenium-containing analogue had a cell line-dependent antioxidant effect against H2O2-induced cytotoxicity: comparable in HepG2 cells and greater in Hep-2 cells. The selenium-containing analogue significantly increased the death of MCF-7 cells at concentrations above 50 µM. The sulphur-containing analogue has lower biological activity as compared to potassium phenosan and the selenium-containing analogue.

5-Aryl-2-(3,5-dialkyl-4-hydroxyphenyl)-4,4-dimethyl-4H-imidazole 3-Oxides and Their Redox Species: How Antioxidant Activity of 1-Hydroxy-2,5-dihydro-1H-imidazoles Correlates with the Stability of Hybrid Phenoxyl-Nitroxides.

Cyclic nitrones of the imidazole series, containing a sterically hindered phenol group, are promising objects for studying antioxidant activity; on the other hand, they can form persistent hybrid phenoxyl-nitroxyl radicals (HPNs) upon oxidation. Here, a series of 5-aryl-4,4-dimethyl-4H-imidazole 3-oxides was obtained by condensation of aromatic 2-hydroxylaminoketones with 4-formyl-2,6-dialkylphenols followed by oxidation of the initially formed N-hydroxy derivatives. It was shown that the antioxidant activity of both 1-hydroxy-2,5-dihydroimidazoles and 4H-imidazole 3-oxides increases with a decrease in steric volume of the alkyl substituent in the phenol group, while the stability of the corresponding HPNs generated from 4H-imidazole 3-oxides reveals the opposite tendency.

Water-soluble phenol TS-13 combats acute but not chronic inflammation.

OBJECTIVE: This study was conducted to evaluate the effect of the synthetic water-soluble phenolic antioxidant TS-13 (sodium 3-(4'-methoxyphenyl)propyl thiosulfonate), an inducer of the redox-dependent Keap1/Nrf2/ARE signaling system, in experimental models of acute and chronic inflammation. METHODS: Acute local inflammation was induced by intraplantar carrageenan injection into rat hind paws, and acute systemic inflammation was modeled by intravenous zymosan injection (in rats) or LPS-induced endotoxic shock (in mice). Chronic inflammation was investigated in rat models of air pouch and collagen-induced arthritis. The effects of TS-13 treatment were estimated by changes in the intensity of inflammation (paw edema, liver infiltration, animal survival, exudation, and clinical score of arthritis) and by the effects on reactive oxygen species (ROS) generation by leukocytes from peripheral blood and inflammatory exudates. RESULTS: We found the significant increase in expression of mRNA, content of protein and activity of a well-characterized Nrf2 target enzyme glutathione S-transferase P1, as well as nuclear extract protein binding to the ARE consensus sequence in liver of mice fed with diet containing TS-13. TS-13 markedly attenuated carrageenan-induced paw edema, reduced blood granulocyte number and volume density of liver infiltrates in the systemic zymosan-induced inflammation model, and increased mice survival after lipopolysaccharide-induced septic shock. However, TS-13 administration did not influence cell and protein exudation into air pouches and suppressed clinical manifestation of collagen-induced polyarthritis only at early stages. Nevertheless, TS-13 inhibited the generation of ROS by leukocytes in all inflammation models. CONCLUSION: The data suggest that the anti-inflammatory effects of Keap1/Nrf2/ARE system are more prominent against acute innate-mediated inflammation than chronic immune inflammation. This narrows the potential therapeutic efficacy of ARE inducers in inflammation treatment.