PJS Vol 135 No. 2, December 2006
Page 83-92
ISSN 0031-7683 



A Modified Procedure for the Preparation of Mitoxantrone




The anticancer drug mitoxantrone is commercially prepared in four synthetic steps starting from readily available chrysazin.  A new and modified procedure for a similar process of mitoxantrone preparation has been successfully applied in small-scale preparation of mitoxantrone in our laboratories.  This new process was designed to be practicable under  Philippine setting.  Success of the synthesis was established by full physico-chemical and spectral characterization of all intermediates and of the final mitoxantrone product.  The cytotoxic activity of the synthesized mitoxantrone was tested against MCF-7 breast cancer cell lines and was found to be similar to commercially available mitoxantrone.





CHANG P. 1992. Synthesis and Characterization of Anticancer Anthraquinones: Ametantrone and Mitoxantrone. Proc Natl Sci Counc ROC(A) 16(4): 304-310.

CHANG P, CHEM KC, KING ML. 1990. Highperformance liquid chromatographic determination of ametantrone and mitoxantrone. Zhonghua Yaoxue Zazhi 42: 129-135.

CHANG P AND CHENG CC. 1995. An Improved Practical Synthesis of Leuco-1,4,5,8-Tetrahydroxyanthraquinone. Synth Commun 25(13): 1893-1900.

CHENG CC AND ZEE-CHENG RKY. 1978. Antineoplastic agents. Structure-activity relationship study of bis(substituted aminoalkylamino)anthraquinones. J Med Chem 21(3): 291-294.

GALINOWSKI S, SWIATLY S, GOGOLEWSKI S, SZAFNICKI W, GUZEWSKA T, KALINOWSKI J, SLACHCUK H, SYNAK J. 1993. 1,8-Dihydroxy4,5- and -2,5-diaminoanthraquinones. Pol PL 126: 191.

IMMUNEX. 1996. FDA Approves Novantrone, Immunex. Immunex Press Release. 13 Nov 1996.

JOHNSON MG, KIYOKAWA H, TANI S, KOYAMA J, MORRIS-NATSCHKE SL, MAUGER A, BOWERS-DAINES MM, LANGE BC, LEE KH. 1997. Antitumor agents-CLXVII. Synthesis and structure-activity correlations of the cytotoxic anthraquinone 1,4-bis-(2,3-epoxypropylamino)-9,10- anthracenedione, and of related compounds. Bioorg Med Chem 5(8): 1469-79.

KRAPCHO AP, GETAHUN Z, AVERY KL, VARGAS KJ, HACKER MP. 1991. Synthesis and antitumor evaluations of symmetrically and unsymmetrically substituted 1,4-bis[(aminoalkyl)amino]anthracene9,10-diones and 1,4-bis[(aminoalkyl)amino]-5,8- dihydroxyanthracene-9,10-diones. J Med Chem 34(8): 2373-80.

MOSSMAN T. 1983. Rapid colorimetric assay for cellular growth and survival: Application to proliferation and cytotoxicity assays. J Immunol Methods 65: 55-63.

MURDOCK K, DURR FE. 1980. 1,4-Bis(substitutedamino)-5,8-dihydroxyanthraquinones and leuco bases thereof. US 4,197,249.

NICLAS HJ, KUNATH A, HEYER T, RUGER C, KONIG J, SOMMER B, OHMANN W, TROBISCH S, ZOLCH Z, LOFFLER R, KORTHALS HP, RAUNER W, SCHWABE K, REDSLOB J. 1983. Verfahren zur Hochreinigung von 1,4-Bis[2-(2-hydroxyethyla mino)ethylamino]-5,8-dihydroxy-9,10-anthrachinon. DD 294390.

POTTER GA, PATTERSON LH, TEESEDALE-SPITTLE P, PANIWYNK Z. 2002. Anthraquinone anticancer drugs. US 6,465,522B1.

POZDNYAKOVICH YV, MOSTOSLAVSKAYA EI, POZDNYAKOVICH SA, BORODOVITSYNA TI, MALAKHOVA TA, MURATOVA LA, SILVER LP, KHOKHLOVA LG, CHUMAK VT. 1995. Method of synthesis of 1,4- dihydroxy - 5,8- bis -((2-((2-hydroxyethyl) - amino) -ethyl) -amino) – anthraquinone. RU 2028290.

SCHWABE K, BEER V, NICLAS HJ, RUEGER C, ZOELCH L, KUNATH A. 1992. Preparation of 1,4-bis[2-(2-hydroxyethylamino)ethylamino]-5,8- dihydroxy-9,10-anthracenedione. DD 300973. Vogelzang NJ. 1996. One Hundred Thirteen Men with Hormone-Refractory Prostate Cancer Died Today. J Clin Oncol 14(6): 1753-55.

ZAGOTTO G, MORO S, URIARTE E, FERRAZZI E, PALU G, PALUMBO M. 1997. Amido analogs of mitoxantrone: physico-chemical properties, molecular modeling, cellular effects and antineoplastic potential. Anti-cancer Drug Design 12: 99-112.

ZAGOTTO G, URIARTE E, ANTONELLO C, CONCONI MT, MAGNO SM, PALUMBO M. 1992. New hydroxy-amido-anthraquinones as potential antineoplastic drugs. Bioorg Med Chem Lett 2: 659-662.