Glutathione conjugates of 2-or 6-substituted 5,8-dimethoxy-1,4-naphthoquinone derivatives: Formation and structure

Thirty-four glutathione conjugates of 5,8-dimethoxy-1,4-naphthoquinones (DM NQ) were synthesized and their structure was determined. The yield of GSH c onjugate was dependent on size of alkyl group; the longer the size of alkyl group was, the lower was the yield. It was also found that the length of a lkyl side chain influenced the chemical shift of quinonoid protons; the qui nonoid protons of 2-glutathionyl DMNQ derivatives with R=H to propyl 6.51-6 .59 ppm Lr. other ones with R=butyl to heptyl, 6.64-6.68 ppm. This was expl ained to be due to a folding effect of longer alkyl group. Glutathione (GSH ) reacted with DMNQ derivative first to form a 1,4-adduct (2- or 3-glutathi onyl-1,4-dihydroxy-5,8-dimethoxynaphthalenes) and then, the adduct was auto oxidized to 2- or 3-glutathionyl-DMNQ derivatives. Moreover, GSH reduced DM NQ derivatives to their hydrogenated products. It was suggested that such a n organic reaction might play an important role for a study of metabolism o r toxicity of DMNQ derivatives in the living cells.