An EPR Study of Free Radicals Formed by Antipsoriatic and Tumor-Promoting 9-Anthrones in Nonpolar Solvents

Abstract

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.

Antioxidants attenuate anthralin-induced skin inflammation in BALB/c mice: role of specific proinflammatory cytokines

“…Anthralin generates reactive oxygen species as well as anthralin radicals, both of which can presumably cause tissue damage [23,24]. Using human keratinocyte cultures, we have shown previously that the oxidative stress associated with anthralin treatment is largely responsible for the expression of proinflammatory cytokines [12].…”

Location of anthralin radical generation in mouse skin by UV‐A irradiation: An estimation using microscopic EPR spectral‐spatial imaging

“…Both the therapeutic and side effects of anthralin are considered to arise from anthralin‐derived free radicals generated in vivo by UV‐irradiation and/or various oxidation processes (7–10). The 1,8‐dihydroxy‐9‐anthrone‐10‐yl radical, which is generated in pure organic solvents by thermolysis or photolysis of anthralin, has been detected by EPR spectroscopy (11). The 1,8‐dihydroxy‐9‐anthrone‐10‐yl radical is not observed in aqueous alkaline solutions.…”