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Usage

Uses

Used in Cancer Therapy:
Ametantrone is used as a chemotherapeutic agent for the treatment of various types of cancer. Its ability to inhibit topoisomerase II and induce DNA damage makes it a potential candidate for cancer treatment. It has been shown to inhibit tumor growth in a Ridgway osteogenic sarcoma mouse model when administered at a dose of 5 mg/kg. However, its effectiveness may vary depending on the type of cancer, as it has been observed to increase tumor growth in mouse models of mammary adenocarcinoma and colon adenocarcoma 11a.
Used in Cancer Research:
Ametantrone is used as a research tool to study the role of topoisomerase II in DNA replication, transcription, and cancer development. Its ability to induce double-strand breaks in SV40 DNA in the presence of topoisomerase II and single-strand breaks in DNA in NCI H187 cells makes it a valuable compound for investigating the mechanisms of DNA damage and repair. Additionally, its cytotoxic effects on NCI H187 and HL-60 cells provide insights into the development of novel anticancer therapies.
Used in Drug Development:
Ametantrone serves as a starting point for the development of new drugs targeting topoisomerase II and other DNA-related enzymes. Its unique properties, such as inducing DNA damage and inhibiting tumor growth in certain cancer models, can be leveraged to design more effective and targeted therapies. Researchers can use Ametantrone as a template to develop new compounds with improved efficacy, selectivity, and reduced side effects.

InChI:InChI=1/C22H28N4O4.2C2H4O2/c27-13-11-23-7-9-25-17-5-6-18(26-10-8-24-12-14-28)20-19(17)21(29)15-3-1-2-4-16(15)22(20)30;2*1-2(3)4/h1-6,23-28H,7-14H2;2*1H3,(H,3,4)

Upstream product

• 28736-42-7 1,4-difluoroanthracene-9,10-dione 
• 111-41-1 2-(2-Aminoethylamino)ethanol 
• 4471-41-4 1,4-bis-(2-hydroxyethylamino)anthraquinone 
• 17648-03-2 9,10-Dihydroxy-2,3-dihydro-anthracene-1,4-dione 
• 141-43-5 ethanolamine 
• 111228-28-5 1,4-bis<<2-<(p-toluenesulfonyl)oxy>ethyl>amino>anthracene-9,10-dione 

Relevant academic research and scientific papers

Ametantrone-based compounds as potential regulators of Tau pre-mRNA alternative splicing

Tau pre-mRNA contains a stem-loop structure involved in the regulation of the alternative splicing of tau protein. We describe here a new family of Tau RNA ligands selected by dynamic combinatorial chemistry based on the combination of ametantrone with small RNA-binding molecules. The most promising compound results from derivatization of one of the side chains of the anthraquinone ring with the small aminoglycoside neamine through a short spacer. This compound binds the RNA target with a high affinity in a preferred binding site, in which the heteroaromatic moiety intercalates in the bulged region of the stem-loop and its side chains and neamine interact with the major groove of the RNA. Importantly, binding of this compound to mutated RNA sequences involved in the onset of some tauopathies such as FTDP-17 restores their thermodynamic stability to a similar or even higher levels than that of the wild-type sequence, thereby revealing its potential as a modulator of Tau pre-mRNA splicing.

Synthesis and tau RNA binding evaluation of ametantrone-containing ligands

We describe the synthesis and characterization of ametantrone-containing RNA ligands based on the derivatization of this intercalator with two neamine moieties (Amt-Nea,Nea) or with one azaquinolone heterocycle and one neamine (Amt-Nea,Azq) as well as its combination with guanidinoneamine (Amt-NeaG4). Biophysical studies revealed that guanidinylation of the parent ligand (Amt-Nea) had a positive effect on the binding of the resulting compound for Tau pre-mRNA target as well as on the stabilization upon complexation of some of the mutated RNA sequences associated with the development of tauopathies. Further studies by NMR revealed the existence of a preferred binding site in the stem-loop structure, in which ametantrone intercalates in the characteristic bulged region. Regarding doubly-functionalized ligands, binding affinity and stabilizing ability of Amt-Nea,Nea were similar to those of the guanidinylated ligand, but the two aminoglycoside fragments seem to interfere with its accommodation in a single binding site. However, Amt-Nea,Azq binds at the bulged region in a similar way than Amt-NeaG4. Overall, these results provide new insights on fine-tuning RNA binding properties of ametantrone by single or double derivatization with other RNA recognition motifs, which could help in the future design of new ligands with improved selectivity for disease-causing RNA molecules.

MEANS FOR DYEING AND/OR MATTING KERATINIC FIBRES CONTAINING NOVEL 1,4 DIAMINOANTHRAQUINONE DYES

Agents for coloring and/or matting keratinic fibers, in particular human hair, include in a cosmetic carrier at least one specific substituted 1,4-diaminoanthraquinone derivative of formula (I), wherein the residues (R2, R4) mutually independently denote a grouping of formula (II). The cosmetic method of using these agents can be for producing intense blue shades and for matting keratin fibers.

Rational design, synthesis, and DNA binding properties of novel sequence-selective peptidyl congeners of ametantrone

Natural and synthetic compounds characterized by an anthraquinone nucleus represent an important class of anti-neoplastic agents, the mechanism of action of which is related to intercalation into DNA. Ametantrone (AM) is a synthetic 9,10-anthracenedione bearing two (hydroxyethylamino)ethylamino residues at positions 1 and 4; along with other anthraquinones and anthracyclines, it shares a polycyclic intercalating moiety and charged side chains that stabilize DNA binding. All these drugs elicit adverse side effects, which represent a challenge for antitumor chemotherapy. In the present work the structure of AM was augmented with appropriate groups that target well-defined base pairs in the major groove. These should endow AM with DNA sequence selectivity. We describe the rationale for the synthesis and the evaluation of activity of a new series of compounds in which the planar anthraquinone is conjugated at positions 1 and 4 through the side chains of AM or other bioisosteric linkers to appropriate dipeptides. The designed novel AM derivatives were shown to selectively stabilize two oligonucleotide duplexes that both have a palindromic GC-rich hexanucleotide core, but their stabilizing effects on a random DNA sequence was negligible. In the case of the most effective compound, the 1,4-bis-[Gly-(l-Lys) ] derivative of AM, the experimental results confirm the predictions of earlier theoretical computations. In contrast, AM had equal stabilizing effects on all three sequences and showed no preferential binding. This novel peptide derivative can be classified as a strong binder regarding the sequences that it selectively targets, possibly opening the exploitation of less cytotoxic conjugates of AM to the targeted treatment of oncological and viral diseases.

Synthesis and Antitumor Evaluations of Symmetrically and Unsymmetrically Substituted 1,4-Bisanthracene-9,10-diones and 1,4-Bis-5,8-dihydroxyanthracene-9,10-diones

The ipso bis displacements of fluoride from 1,4-difluoroanthracene-9,10-dione (3) and 1,4-difluoro-5,8-dihydroxyanthracene-9,10-dione (4) by excess of a diamine (or a monoamine) in pyridine at room temperature lead to the symmetrically substituted 1,4-bis-substituted analogues 5 and 6, respectively.The ipso monodisplacements of fluoride from 3 and 4 can be accomplished by treatment with less than 1 molar equiv of a diamine (or a monoamine) to yield 7 and 8, respectively.Treatment of 7 or 8 with a different diamine leads to the unsymmetrically substituted1,4-bisanthracene-9,10-diones 9 and 10, respectively.Many of the synthetic unsymmetrical analogues have been evaluated for their antitumor activity against L1210 in vitro and in vivo.Cross resistance of analogue 10a with mitoxantrone (2) and doxorubicin was evaluated against MDR lines in vitro against human colon carcinoma LOVO and its subline resistant to DOXO (LOVO/DOXO).Potential mechanisms for the observed cytotoxicity are presented and discussed.