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Structure and tumor-promoting activity of analogues of anthralin (1,8-dihydroxy-9-anthrone)
Abstract:
Seventeen analogues of the tumor-promoting agent anthralin were tested for the same biological property by repeated skin application on mouse skin using female ICR/Ha Swiss mice, after a single application of a subcarcinogenic dose of 7,12-dimethylbenz[a]anthracene. Seven of the compounds tested are new compounds. They are 1,8-diacetoxy-9-anthrone, 1,8-dimyristoyloxy-9-anthrone, 1,8-dihydroxy-10-acetyl-9-anthrone, 1,8-dihydroxy-10-myristoyl-9-anthrone, 1,8,10-trihydroxy-9-anthrone, 1,8-dihydroxy-9,10-dihydroanthracene, and myristoyljuglone. All compounds were used in pure form for the bioassays. Of the 17 test compounds four showed notable tumor-promoting activity. They are 1,8-dihydroxy-10-acetyl-9-anthrone, 1,8-dihydroxy-10-myristoyl-9-anthrone, 1-hydroxy-9-anthrone, and juglone. In order to determine whether there is any relationship between tumor-promoting activity and metal chelation in this series, the chelating abilities of anthralin and of its inactive analogue 1,8-dihydroxyanthraquinone were examined using the bivalent metal ions Cu(II), Zn(II), Mn(II), Mg(II), and Ca(II). No relationship between chelation and tumor-promoting ability was found.
Insights
Four anthralin analogues demonstrated significant tumor-promoting activity in mouse skin models. Metal chelation ability did not correlate with this tumor-promoting property in the tested compounds.
Area of Science:
- Chemical carcinogenesis
- Dermatology
- Toxicology
Background:
- Anthralin is a known tumor-promoting agent.
- Investigating structural analogues of anthralin is crucial for understanding structure-activity relationships in chemical carcinogenesis.
- Identifying novel tumor promoters aids in developing preventative strategies.
Purpose of the Study:
- To synthesize and evaluate seventeen anthralin analogues for tumor-promoting activity.
- To investigate the potential correlation between metal chelation and tumor-promoting effects.
- To identify specific structural features responsible for tumor promotion.
Main Methods:
- Synthesis of seven novel anthralin analogues.
- Repeated topical skin application of compounds on female ICR/Ha Swiss mice pre-treated with 7,12-dimethylbenz[a]anthracene.
- Assessment of tumor-promoting activity of 17 compounds.
- Evaluation of metal chelating abilities of selected compounds with bivalent metal ions (Cu(II), Zn(II), Mn(II), Mg(II), Ca(II)).
Main Results:
- Four out of seventeen tested anthralin analogues exhibited notable tumor-promoting activity.
- The active compounds identified were 1,8-dihydroxy-10-acetyl-9-anthrone, 1,8-dihydroxy-10-myristoyl-9-anthrone, 1-hydroxy-9-anthrone, and juglone.
- No significant correlation was found between the metal chelating abilities of anthralin and its analogue and their tumor-promoting activity.
Conclusions:
- Specific anthralin analogues possess significant tumor-promoting potential.
- Metal chelation does not appear to be a key mechanism underlying the tumor-promoting activity of these anthralin derivatives.
- Further research into the structural determinants of tumor promotion in this series is warranted.