An EPR study of free radicals formed by antipsoriatic and tumor-promoting 9-anthrones in nonpolar solvents.
Certain 9-anthrone derivatives are useful in treating psoriasis and are also known to be tumor promoters in mouse skin. Their therapeutic use is accompanied by side effects of severe skin inflammation, irritation, and staining. The precise biochemical mechanisms of therapeutic action, tumor promotion, and side effects are presently uncertain, although the corresponding 9-anthron-10-yl radicals have been proposed as important intermediates. In order to gain insight into the possible role of anthrone-derived radicals in mediating the biological effects of these compounds, in the present study free radicals from a number of anthrone derivatives were generated by thermolysis in nonpolar solvents. Hyperfine splitting constants (hfsc) of the radicals were determined by electron paramagnetic resonance (EPR) spectroscopy. The experimentally determined hfsc's were also compared with spin densities obtained by molecular calculations (MOPAC 6.0). The experimental and theoretical data were found to be consistent in all cases. The formation of 9-anthron-10-yl radicals appears to be a general phenomenon among 9-anthrones regardless of therapeutic or tumor-promoting effectiveness, although there is a trend toward easier radical formation for the more active compounds.
Motten
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AG
Laboratory of Molecular Biophysics, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, North Carolina 27709.
Sik
R H
RH
Chignell
C F
CF
Hayden
P J
PJ
D000287:Administration, Topical; D000873:Anthracenes / Q000737:chemistry*; D000893:Anti-Inflammatory Agents / Q000737:chemistry; D002273:Carcinogens / Q000737:chemistry*; D004578:Electron Spin Resonance Spectroscopy; D005609:Free Radicals / Q000737:chemistry; D011565:Psoriasis / Q000188:drug therapy; D012997:Solvents; D013329:Structure-Activity Relationship
D000873:Anthracenes; D000893:Anti-Inflammatory Agents; D002273:Carcinogens; D005609:Free Radicals; D012997:Solvents; C013883:chrysarobin