Disease relevance of Ametantrone

• The cytotoxic efficacies of several substituted anthraquinones, ametantrone, dihydroxyanthracenedione, dihydroxyanthracenedione diacetate, mitoxantrone, bisantrene, and doxorubicin, were evaluated on an established human colon adenocarcinoma cell line by the method of inhibition of colony formation [1].
• Potent activity was demonstrated in vitro against murine L1210 leukemia cells (equipotent with ametantrone) as well as against P388 leukemia in vivo (% T/C = 130-255) [2].
• Because of the partial response seen in one patient with renal cell carcinoma, Phase II trials should include this tumor category in order to better define the activity of ametantrone in this disease [3].
• Preclinical toxicity of the new antineoplastic agent, ametantrone acetate, in mice and dogs [4].
• Comparison of mitoxantrone and ametantrone in human acute myelocytic leukemia cells in culture and in bone marrow granulocyte-macrophage progenitor cells [5].

High impact information on Ametantrone

• 1,4-Diamino-substituted anthraquinone antitumor agents (mitoxantrone and ametantrone) and structurally related 1,5- and 1,8-diamino-substituted compounds (AM1 and AM2) were tested for their ability to photosensitize human leukemic cells in culture [6].
• Mitoxantrone and ametantrone inhibited NADPH-cytochrome P-450 reductase- and xanthine oxidase-catalyzed conjugated diene formation from linoleic acid in a concentration-dependent manner with half-maximal inhibition achieved at approximately 0.5 microM anthracenedione [7].
• Under aerobic conditions, the interaction of DCFH2 with pyocyanin or phenazine methosulfate (but not mitoxantrone or ametantrone) produced superoxide, as detected by spin trapping [8].
• In the present study we examined the ultrastructural modifications as well as the precise distribution of DNA and RNA in RT4 cell nucleoli following a 3-h exposure to nontoxic or toxic doses of ametantrone (AMT), poly(adenylate-uridylate) (polyr(A-U), or an AMT/polyr(A-U) combination [9].
• The peptidyl anthraquinones maintain the ability of intercalating efficiently into DNA, even though the orientation within the base-pair pocket may change somewhat with reference to the parent drugs mitoxantrone (MX) and ametantrone (AM) [10].

Biological context of Ametantrone

• The anthracenediones however, completely inhibited mitochondrial lipid peroxidation Drug-stimulated lipid peroxidation was also effectively diminished by mitoxantrone and ametantrone in a concentration-dependent manner [11].
• Kinetics of the binding of mitoxantrone, ametantrone and analogues to DNA: relationship with binding mode and anti-tumour activity [12].
• Pharmacokinetics of ametantrone acetate (NSC-287513) [13].
• Teratology studies of ametantrone acetate in rats and rabbits [14].

Anatomical context of Ametantrone

• Mitoxantrone was able to displace dimethylbenzanthracene bound microsomes with a linear representation of one ligand-one acceptor model, whereas bimodal shape was found in the case of ametantrone [15].
• The overall in vitro response rates (defined as a less than or equal to 50% survival of tumor colony-forming units) for TMQ were 20% and 23% at 0.1 and 1 microgram/ml, respectively; for ametantrone they were 13%, 21%, and 26% at 0.1, 1, and 10 micrograms/ml, respectively [16].
• Both mitoxantrone and ametantrone were more cytocidal on normal bone marrow CFU-GM than on AML cells; mitoxantrone was approximately 2.5-fold and ametantrone nearly 10-fold more active against CFU-GM than against HL-60 AML cells [5].

Associations of Ametantrone with other chemical compounds

• The relative inability of the anthracenediones to stimulate lipid peroxidation is consistent with the diminished cardiotoxicity of ametantrone and mitoxantrone relative to doxorubicin and daunorubicin [11].
• Mitoxantrone and ametantrone also protected against rat microsomal lipid peroxidation produced by nitrofurantoin, paraquat and doxorubicin, decreasing these rates by 80, 90, and 50%, respectively, at 10 microM anthracenedione [11].
• The anthraquinone-based antitumour agents mitoxantrone, daunorubicin and ametantrone were found to be substrates for NAD(P)H (quinone acceptor) oxidoreductase (DT-diaphorase) [QAO] isolated from rat liver [17].
• The pharmacokinetic parameters for ametantrone acetate (CI-881) were characterized in six patients concurrently with the phase I clinical trial [13].
• Redox potential, superoxide production and NADH dehydrogenase substrate properties of daunorubicin, its four sugar-modified derivatives, 4-demethoxydaunorubicin and ametantrone have been examined [18].

Gene context of Ametantrone

• Unlike ametantrone, the compounds have shown to be able to overcome the multidrug resistance [19].
• In the presence of benzo[alpha]-pyrene, mitoxantrone enhanced microsomal NADPH oxidation by 21%, whereas ametantrone produced a 22% decrease in cofactor oxidation relative to the control rate [20].

Analytical, diagnostic and therapeutic context of Ametantrone

• High-performance liquid chromatography was carried out to quantitate mitoxantrone using ametantrone as internal standard [21].
• Ametantrone inhibits prostaglandin--mediated resorption in bone organ culture [22].
• 1,4-dihydroxy-5-bis[[2-[(2-hydroxyethyl)amino]ethyl]amino]-9,10-anthracenedione one (NSC 287836) and 1,4-bis[[2-[(2-hydroxyethyl)amino]ethyl]amino]-9,10-anthracenedione diacetate (NSC 287513) have shown activity against solid tumors and are now in Phase I clinical trials [23].

References