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Synthesis and antiproliferative activity of 1,4-bis(dimethylamino)-9,10-anthraquinone derivatives against P388 mouse leukemic tumor cells

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Abstract

A series of 2-substituted-1,4-bis(dimethylamino)-9,10-anthraquinone derivatives were synthesized and their in vitro antiproliferative activities against p388 mouse leukemic tumor cells were evaluated. In addition, the effect of substituents on the phenyl ring was investigated. Among the derivatives tested, seven showed a high antiproliferative effect and three showed a moderate effect. In addition, introduction of a series of substituted phenyl groups into 1,4-bis(dimethylamino)-9,10-anthraquinone at 2-position were shown to enhance its antiproliferative activity. The antiproliferative activity also increased upon substitution of the benzene ring by an electron donating group such as an amine or methoxyl group.

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References

  • Berthiaume, J. M. and Wallace, K. B., Adriamycin-induced oxidative mitochondrial cardiotoxicity. Cell Biol. Toxicol., 23, 15–25 (2007).

    Article  PubMed  CAS  Google Scholar 

  • Capranico, G., Palumbo, M., Tinelli, S., Mabilia, M., Pozzan, A., and Zunino, F., Conformational drug determinants of the sequence specificity of drug-stimulated topoisomerase II DNA cleavage. J. Mol. Biol., 235, 1218–1230 (1994).

    Article  PubMed  CAS  Google Scholar 

  • Cheng, C. C. and Zee-Cheng, R. K., The design, synthesis and development of a new class of potent antineoplastic anthraquinones. Prog. Med. Chem., 20, 83–118 (1983).

    Article  PubMed  CAS  Google Scholar 

  • Dal Ben, D., Palumbo, M., Zagotto, G., Capranico, G., and Moro, S., DNA topoisomerase II structures and anthracycline activity: insights into ternary complex formation. Curr. Pharm. Des., 13, 2766–2780 (2007).

    Article  Google Scholar 

  • Fisher, G. R., Gutierrez, P. L., Oldcorne, M. A., and Patterson, L. H., NAD(P)H (quinone acceptor) oxidoreductase (DT-diaphorase)-mediated two-electron reduction of anthraquinone-based antitumour agents and generation of hydroxyl radicals. Biochem. Pharmacol., 43, 575–585 (1992).

    Article  PubMed  CAS  Google Scholar 

  • Gatto, B., Zagotto, G., Sissi, C., Cera, C., Uriarte, E., Palù, G., Capranico, G., and Palumbo, M., Peptidyl anthraquinones as potential antineoplastic drugs: synthesis, DNA binding, redox cycling, and biological activity. J. Med. Chem., 39, 3114–3122 (1996).

    Article  PubMed  CAS  Google Scholar 

  • Hsiao, C. J., Li, T. K., Chan, Y. L., Hsin, L. W., Liao, C. H., Lee, C. H., Lyu, P. C., and Guh, J. H., WRC-213, an l-methionine-conjugated mitoxantrone derivative, displays anticancer activity with reduced cardiotoxicity and drug resistance: identification of topoisomerase II inhibition and apoptotic machinery in prostate cancers. Biochem. Pharmacol., 75, 847–856 (2008).

    Article  PubMed  CAS  Google Scholar 

  • Jin, G. Z., Kim, Y., Chung, J. H., Sok, D. E., and Ahn, B. Z., Anthracene-1,4,9,10-tetraone derivatives: synthesis and antitumor activity. Arch. Pharm. (Weinheim), 331, 380–384 (1998a).

    Article  CAS  Google Scholar 

  • Jin, G. Z., Song, G. Y., Zheng, X. G., Kim, Y., Sok, D. E., and Ahn, B. Z., 2-(1-Oxyalkyl)-1,4-dioxy-9,10-anthraquinones: synthesis and evaluation of antitumor activity. Arch. Pharm. Res., 21, 198–206 (1998b).

    Article  PubMed  CAS  Google Scholar 

  • Jin, G. Z., You, Y. J., and Ahn, B. Z., Esters of 2-(1-hydroxyalkyl)-1,4-dihydroxy-9,10-anthraquinones with melphalan as multifunctional anticancer agents. Bioorg. Med. Chem. Lett., 11, 1473–1476 (2001a).

    Article  PubMed  CAS  Google Scholar 

  • Jin, G. Z., You, Y. J., Kim, Y., Nam, N. H., and Ahn, B. Z., Esters of chlorambucil with 2-substituted 1,4-dihydroxy-9,10-anthraquinones as multifunctional anticancer agents. Eur. J. Med. Chem., 36, 361–366 (2001b).

    Article  PubMed  CAS  Google Scholar 

  • Loadman, P. M., Swaine, D. J., Bibby, M. C., Welham, K. J., and Patterson, L. H., A preclinical pharmacokinetic study of the bioreductive drug AQ4N. Drug Metab. Dispos., 29, 422–426 (2001).

    PubMed  CAS  Google Scholar 

  • Perchellet, E. M., Magill, M. J., Huang, X., Dalke, D. M., Hua, D. H., and Perchellet, J. P., 1,4-Anthraquinone: an anticancer drug that blocks nucleoside transport, inhibits macromolecule synthesis, induces DNA fragmentation, and decreases the growth and viability of L1210 leukemic cells in the same nanomolar range as daunorubicin in vitro. Anticancer Drugs, 11, 339–352 (2000).

    Article  PubMed  CAS  Google Scholar 

  • Piedade, J. A., Fernandes, I. R., and Oliveira-Brett, A. M., Electrochemical sensing of DNA-adriamycin interactions. Bioelectrochemistry, 56, 81–83 (2002).

    Article  PubMed  CAS  Google Scholar 

  • Sadeghi-Aliabadi, H., Tabarzadi, M., and Zarghi, A., Synthesis and cytotoxic evaluation of two novel anthraquinone derivatives. Farmaco, 59, 645–649 (2004).

    Article  PubMed  CAS  Google Scholar 

  • Silverman, R. B., The Organic Chemistry of Drug Design and Drug Actionf. Elsevier Academic Press, USA, (2004).

    Google Scholar 

  • Tam, M. N., Nam, N. H., Jin, G. Z., Song, G. Y., and Ahn, B. Z., Synthesis and evaluation of the antitumor activity of 2-substituted 1,4-dihydroxy-9,10-anthraquinones. Arch. Pharm. (Weinheim), 333, 189–194 (2000).

    Article  CAS  Google Scholar 

  • Teich, L., Daub, K. S., Krügel, V., Nissler, L., Gebhardt, R., and Eger, K., Synthesis and biological evaluation of new derivatives of emodin. Bioorg. Med. Chem., 15, 5961–5971 (2004).

    Article  Google Scholar 

  • Trieb, M., Rauch, C., Wellenzohn, B., Wibowo, F., Loerting, T., Mayer, E., and Liedl, K. R., Daunomycin intercalation stabilizes distinct backbone conformations of DNA. J. Biomol. Struct. Dyn., 21, 713–724 (2004).

    PubMed  CAS  Google Scholar 

  • Tütem, E., Apak, R., and Sözgen, K., The interaction of antitumor-active anthraquinones with biologically important redox couples: I. Spectrophotometric investigation of the interaction of carminic acid and mitoxantrone with the iron (II, III) and copper (I, II) redox couples. J. Inorg. Biochem., 61, 79–96 (1996).

    Article  PubMed  Google Scholar 

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Correspondence to Guang-Zhu Jin.

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Jin, GZ., Jin, HS. & Jin, LL. Synthesis and antiproliferative activity of 1,4-bis(dimethylamino)-9,10-anthraquinone derivatives against P388 mouse leukemic tumor cells. Arch. Pharm. Res. 34, 1071–1076 (2011). https://doi.org/10.1007/s12272-011-0704-0

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  • DOI: https://doi.org/10.1007/s12272-011-0704-0

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