Antioxidant and antiinflammatory activity of new water-soluble sulfur-containing phenolic compounds.

We synthesized a series of structurally related water-soluble alkyl phenols - sodium 4-hydroxyphenyl propyl sulfonates and thiosulfonates with different number of tert-butyl groups at the ortho-position. In experimental systems of transient metal-induced ethyl oleate and low-density lipoprotein oxidation the antioxidant activity of the compounds increased when the tert-butyl group number at the ortho-position increased and when the sulfonate group was replaced with thiosulfonate. Compounds containing thiosulfonate group in para-propyl substituent also more effectively inhibited reactive oxygen metabolites generated in xanthine-xanthine oxidase system and during morpholinosydnonimine decomposition compared to sulfonate-containing analogs. Phenols with one tert-butyl group at the ortho-position have been shown to exhibit the highest antiinflammatory activity in the model of carrageenan-induced rat paw inflammation, as well as with regard to the expression of the glutathione S-transferase P1-1 gene in HepG2 human hepatoma cell line. Thus, it can be reasonably speculated that the antiinflammatory activity of sulfur-containing phenolic antioxidants in vivo is mediated by their effect on redox-sensitive transcription factors.