Disease relevance of Anthracenedione

• Phase II trial of docetaxel in advanced anthracycline-resistant or anthracenedione-resistant breast cancer [1].
• Photosensitization of human leukemic cells by anthracenedione antitumor agents [2].
• Mitoxantrone, a cytotoxic anthracenedione derivative, has given clinical evidence of beneficial activity in breast cancer, lymphoma and leukaemia [3].
• Mitoxantrone hydrochloride, a synthetic anthracenedione approved for worsening relapsing-remitting multiple sclerosis and secondary progressive multiple sclerosis, has been shown to primarily suppress the humoral response [4].
• Benzothiopyranoindazoles, a new class of chromophore modified anthracenedione anticancer agents. Synthesis and activity against murine leukemias [5].

High impact information on Anthracenedione

• 1,4-Dihydroxy-5,8-bis(( (2-[(2-hydroxyethyl)amino]ethyl)-amino))-9,10-anthracenedione dihydrochloride is a new anthracenedione derivative that was evaluated in a Phase I clinical trial [6].
• The anthracenedione antineoplastic agents mitoxantrone and ametantrone are potent inhibitors of basal and drug-stimulated lipid peroxidation in a variety of subcellular systems (Kharasch, E. D., and Novak, R. F. (1983) J. Pharmacol. Exp. Ther. 226, 500-506) [7].
• Mitoxantrone, an anthracenedione synthetic agent, was also shown to be effective as treatment for active SP-MS [8].
• Thirty-five patients with hepatocellular carcinoma (HCC) have been treated with the Anthracenedione derivative, Mitozantrone [9].
• In this study, BBR 2778, BBR 2378, and an anthracenedione compound, 1,4-bis[(2-aminoethyl)amino]-5,8-dimethyl-9,10-anthracenedione, were used to assess the relationship between the chemical structures of these drugs and their interactions with DNA and P-gp [10].

Chemical compound and disease context of Anthracenedione

• As mitoxantrone is a recently approved immunosuppressant for managing multiple sclerosis, the number of patients treated with this effective but potentially cardiotoxic anthracenedione derivative will increase substantially [11].
• Although advancing age has been reported to be a poor prognostic factor in ANLL, recent clinical trials have shown good results in patients aged 60 years and over after coadministration of the anthracenedione antineoplastic agent mitoxantrone with cytarabine [12].

Biological context of Anthracenedione

• Although the mechanism underlying partial reversion to a drug-sensitive phenotype in the original Vtgm-6 hybrid lines has yet to be defined, the data obtained in these lines indicate that anthracycline- and anthracenedione-induced cytotoxic effects can be dissociated from DNA cleavage activity [13].
• Thus, there appears to exist a structural relationship between anthracenedione ring hydroxylation and metabolic activation [14].
• The hepatobiliary pharmacokinetics of mitoxantrone, a new anthracenedione derivative, was studied in the isolated perfused rat liver [15].
• The only difference in the molecular structure (other than the nature of their amine salts) between dihydroxyanthracenedione and anthracenedione acetate lies in the para-hydroxyl groups in the ring adjacent to the quinone ring [16].
• Relationship between cytotoxicity and DNA damage in mammalian cells treated with anthracenedione derivatives [17].

Anatomical context of Anthracenedione

• The ability of HAQ, a prototypic anthracenedione, to inhibit PG synthesis and PG-mediated bone resorption was investigated using neonatal mouse calvaria in organ culture [18].
• The effects of two anthracenedione derivatives on in vitro cell survival and DNA of Chinese hamster ovary (CHO) cells were investigated [17].
• The results of the MTT assay showed a high degree of correlation with those of the HTCA in predicting the sensitivity of cancer cell lines to platinum analogues, and anthracyclines/anthracenedione [19].

Associations of Anthracenedione with other chemical compounds

• Ametantrone acetate is an intensely blue anthracenedione undergoing clinical trials in man [20].
• Rabbit cardiac sarcosomal NADPH-dependent lipid peroxidation was inhibited completely at 100 microM anthracenedione [21].
• The effects of mitoxantrone, ametantrone and a monohydroxylated anthracenedione on hepatic microsomal, cardiac sarcosomal and cardiac mitochondrial lipid peroxidation were examined and compared with those of doxorubicin and daunorubicin [22].
• Inhibition of adriamycin-stimulated microsomal lipid peroxidation by mitoxantrone and ametantrone, two new anthracenedione antineoplastic agents [23].

Gene context of Anthracenedione

• Mitoxantrone, an anthracenedione antitumor agent, frequently selects for non-P-glycoprotein-mediated multidrug resistance in in vitro models [24].
• The anthracenedione, mitoxantrone, frequently selects for a unique drug resistance phenotype that is not mediated by either MDR 1, MRP, or altered DNA topoisomerase II [25].
• Two anthracenedione antineoplastic agents, mitoxantrone and the nonhydroxylated analog, ametantrone, were found to inhibit hepatic microsomal cytochrome P-450-dependent drug metabolism in vitro and in vivo [26].

Analytical, diagnostic and therapeutic context of Anthracenedione

• Patients were eligible if they had received one prior chemotherapy regimen with an anthracycline or anthracenedione for metastatic disease, if they had responded to that prior regimen, and if they had relapsed at least 6 months after the first response [27].
• The anthracenedione mitoxantrone was used as part of the 3M/2M regimen in the neoadjuvant trial at the Royal Marsden Hospital, which was the first to establish within the setting of a clinical trial, the reduction in mastectomy requirements [28].

References