Structure and tumor-promoting activity of analogs of anthralin (1,8-dihydroxy-9-anthrone)

• Published in: Journal of medicinal chemistry 1978-01, Vol.21 (1), p.26-31
• Main Authors: Van Duuren, B. L, Segal, A, Tseng, S. S, Rusch, G. M, Loewengart, G, Mate, U, Roth, D, Smith, A, Melchionne, S, Seidman, I
• Format: Article
• Language: English
• Subjects: Animals; Anthracenes - pharmacology; Anthralin - analogs & derivatives; Anthralin - chemical synthesis; Anthralin - pharmacology; Anthraquinones - pharmacology; Chemical Phenomena; Chemistry; Female; Metals; Mice; Mice, Inbred ICR; Neoplasms, Experimental - chemically induced; Skin Neoplasms - chemically induced
• ISSN: 0022-2623; 1520-4804
• DOI: 10.1021/jm00199a005

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.