Detection and characterization of 9-anthron-10-yl radicals formed by antipsoriatic and tumor-promoting 9-anthrones in aqueous buffers.
Certain 1,8-dihydroxy-9-anthrones have been used for the topical treatment of psoriasis for over seventy-five years. The therapeutic usefulness of these compounds is limited, however, by side effects including severe skin inflammation and staining. Antipsoriatic 9-anthrones are also tumor promoters in mouse skin. The chemical mechanisms underlying the biological properties of 9-anthrones are believed to involve the generation of free radical products such as 9-anthron-10-yl radicals or secondary oxygen radicals such as O2.- or OH.. However, the specific role that 9-anthron-10-yl radicals may play in mediating the biological effects of 9-anthrones is uncertain because these species have not been detected in biological systems. In the present study we have used the EPR spin trapping technique to demonstrate for the first time the formation of the 1,8-dihydroxy-9-anthron-10-yl radical in aqueous buffers. Additionally, in order to gain information concerning the role of 9-anthron-10-yl radicals in tumor promotion and antipsoriatic activities, we have used this technique to investigate the formation of these radical species by a series of 9-anthrones of known tumor-promoting and antipsoriatic activities. All of the 9-anthrones studied formed spin adducts with 3,5-dibromo-4-nitrosobenzenesulfonic acid in aqueous buffers. The formation of these adducts was pH-dependent, being favored at alkaline pH.(ABSTRACT TRUNCATED AT 250 WORDS)
Hayden
P J
PJ
Laboratory of Molecular Biophysics, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709.
Chignell
C F
CF
D000873:Anthracenes / Q000032:analysis* / Q000737:chemistry*; D000875:Anthralin / Q000032:analysis; D002021:Buffers; D002273:Carcinogens / Q000737:chemistry*; D004578:Electron Spin Resonance Spectroscopy; D005609:Free Radicals; D006863:Hydrogen-Ion Concentration; D010084:Oxidation-Reduction; D011565:Psoriasis / Q000188:drug therapy*; D013056:Spectrophotometry, Ultraviolet; D013696:Temperature
D000873:Anthracenes; D002021:Buffers; D002273:Carcinogens; D005609:Free Radicals; D000875:Anthralin