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.
Zenkov
N K
NK
Scientific Center of Clinical and Experimental Medicine, Siberian Branch of the Russian Academy of Medical Sciences, Novosibirsk 630117, Russia.
Menshchikova
E B
EB
Kandalintseva
N V
NV
Oleynik
A S
AS
Prosenko
A E
AE
Gusachenko
O N
ON
Shklyaeva
O A
OA
Vavilin
V A
VA
Lyakhovich
V V
VV
D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000737:chemistry* / Q000494:pharmacology*; D000975:Antioxidants / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D002460:Cell Line; D015870:Gene Expression / Q000187:drug effects; D051549:Glutathione S-Transferase pi / Q000235:genetics / Q000378:metabolism; D006801:Humans; D020128:Inhibitory Concentration 50; D010636:Phenols / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D012995:Solubility; D013457:Sulfur Compounds / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D014867:Water / Q000737:chemistry
D000894:Anti-Inflammatory Agents, Non-Steroidal; D000975:Antioxidants; D010636:Phenols; D013457:Sulfur Compounds; D014867:Water; C496556:GSTP1 protein, human; D051549:Glutathione S-Transferase pi