Bisantrene (CL 216942; NSC 337766) is potent inhibitor of topoisomerase II and DNA intercalators. It could be employed as model compounds to investigate multiple drug resistance (MDR1) mediated by P-glycoprotein. You could use bisantrene as a Rac1 inhibitor. DNA single-strand breaks, DNA-protein crosslinking, and the inhibition of DNA replication are all caused by bisantrene intercalating with DNA and altering its configuration. In terms of activity, this agent is comparable to doxorubicin; however, it does not show cardiotoxicity.
Physicochemical Properties
| Molecular Formula | C₂₂H₂₂N₈ |
| Molecular Weight | 398.46 |
| Exact Mass | 398.197 |
| CAS # | 78186-34-2 |
| Related CAS # | 78186-34-2 71439-68-4 (2HCl) 97910-18-4 (4HCl) 97910-19-5 (nitrate) 97910-20-8 (sulfate) 101218-44-4 (acetate) |
| PubChem CID | 5351322 |
| Appearance | Orange to red solid powder |
| Density | 1.41g/cm3 |
| Boiling Point | 646.3ºC at 760 mmHg |
| Flash Point | 344.7ºC |
| Index of Refraction | 1.757 |
| LogP | 2.069 |
| Hydrogen Bond Donor Count | 4 |
| Hydrogen Bond Acceptor Count | 4 |
| Rotatable Bond Count | 6 |
| Heavy Atom Count | 30 |
| Complexity | 630 |
| Defined Atom Stereocenter Count | 0 |
| SMILES | C1NC(=NC1)N/N=C/C2=C3C(=C(C4=CC=CC=C24)/C=N/NC5=NCCN5)C=CC=C3 |
| InChi Key | NJSMWLQOCQIOPE-OCHFTUDZSA-N |
| InChi Code | InChI=1S/C22H22N8/c1-2-6-16-15(5-1)19(13-27-29-21-23-9-10-24-21)17-7-3-4-8-18(17)20(16)14-28-30-22-25-11-12-26-22/h1-8,13-14H,9-12H2,(H2,23,24,29)(H2,25,26,30)/b27-13+,28-14+ |
| Chemical Name | N-[(E)-[10-[(E)-(4,5-dihydro-1H-imidazol-2-ylhydrazinylidene)methyl]anthracen-9-yl]methylideneamino]-4,5-dihydro-1H-imidazol-2-amine |
| Synonyms | Bisantrene; CL216942 |
| HS Tariff Code | 2934.99.9001 |
| Storage |
Powder-20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
| Shipping Condition | Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs) |
Biological Activity
| Targets | Topoisomerase II |
| ln Vitro | At oligonucleotide-oligonucleotide junctions, bisantrene stimulates DNase I cleavage, whereas at alternating purine-nucleotide junctions, it marginally diminishes cleavage activity [1]. Two nucleotides, [3H] uracil and [3H] thoracic, which can be imported into RNA and DNA, respectively, make up bisantrene [2]. |
| ln Vivo | Bisantrene is an antineoplastic agent with activity against a variety of experimental tumors, including P388 white, L1210 white, Lieberman plasmacytoma, B16 melanoma, tumor 26, and Ridgway sarcoblastoma [3]. Bisantrene ranges from 1.56 to 150. Effective within a dose range of mg/kg, depending on the frequency, method and timing of treatment and the tumor model utilized [3]. Bisantrene (25, 50, and 100 mg/kg; i.p.; once) ablate macrophages. Bisantrene (10-150 mg/kg; i.v.; once) induces a profound leukopenia in Neo mice. Anti-tumor effects were shown in mice injected with P815 tumor cells [3]. It is the target of Bisantrene toxicity [4]. |
| Enzyme Assay | In ETN buffer (1 mM EDTA, 10 mM Tris, pH 7.0, with NaCl to obtain the desired ionic strength), measurements are performed at 25°C. Spectrophotometric or fluorometric methods are used to observe binding in the ligand absorption or emission region, respectively, following the addition of scalar quantities of DNA to a newly made drug solution. The range of bound drug fractions is 0.15-0.85 in order to prevent significant systematic errors that could arise from experimental errors in extinction coefficients or fluorescence quantum yield. Data are assessed. A Perkin-Elmer Lambda 5 apparatus and an MPF66 fluorometer, both of which have a Haake F3-C thermostat, are used for spectroscopic measurements[1]. |
| References |
[1]. DNA-binding preferences of Bisantrene analogues: relevance to the sequence specificity of drug-mediated topoisomerase II poisoning. Mol Pharmacol. 1998 Dec;54(6):1036-45. [2]. Bisantrene, an active new drug in the treatment of metastatic breast cancer. Cancer Res. 1983 Mar;43(3):1402-4. [3]. Activation of tumor-cytostatic macrophages with the antitumor agent 9,10-anthracenedicarboxaldehyde bis[(4,5-dihydro-1H-imidazole-2-yl)hydrazone] dihydrochloride (bisantrene). Cancer Res. 1984 Jun;44(6):2363-7. [4]. Retroviral transfer of the human MDR1 gene confers resistance to bisantrene-specific hematotoxicity. Clin Cancer Res. 1996 Jun;2(6):973-80. |
| Additional Infomation |
Bisantrene is an anthracenyl bishydrazone with antineoplastic activity. Bisantrene intercalates with and disrupts the configuration of DNA, resulting in DNA single-strand breaks, DNA-protein crosslinking, and inhibition of DNA replication. This agent is similar to doxorubicin in activity, but unlike doxorubicin, does not exhibit cardiotoxicity. (NCI04) Bisantrene Hydrochloride is the hydrochloride salt of an anthracenyl bishydrazone with antineoplastic activity. Bisantrene intercalates with and disrupts the helical structure of DNA, resulting in DNA single-strand breaks, DNA-protein crosslinking, and inhibition of DNA replication. This agent is similar to doxorubicin in activity, but unlike doxorubicin, does not exhibit cardiotoxicity. |
Solubility Data
| Solubility (In Vitro) |
DMSO: ~1 mg/mL (~2.5 mM) H2O: 0.1 mg/mL (~0.3 mM) |
| Solubility (In Vivo) |
Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples. Injection Formulations (e.g. IP/IV/IM/SC) Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] *Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. Injection Formulation 5: 2-Hydroxypropyl-β-cyclodextrin : Saline = 50 : 50 (i.e. 500 μL 2-Hydroxypropyl-β-cyclodextrin → 500 μL Saline) Injection Formulation 6: DMSO : PEG300 : castor oil : Saline = 5 : 10 : 20 : 65 (i.e. 50 μL DMSO → 100 μLPEG300 → 200 μL castor oil → 650 μL Saline) Injection Formulation 7: Ethanol : Cremophor : Saline = 10： 10 : 80 (i.e. 100 μL Ethanol → 100 μL Cremophor → 800 μL Saline) Injection Formulation 8: Dissolve in Cremophor/Ethanol (50 : 50), then diluted by Saline Injection Formulation 9: EtOH : Corn oil = 10 : 90 (i.e. 100 μL EtOH → 900 μL Corn oil) Injection Formulation 10: EtOH : PEG300：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL EtOH → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Oral Formulations Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). Oral Formulation 3: Dissolved in PEG400 Oral Formulation 4: Suspend in 0.2% Carboxymethyl cellulose Oral Formulation 5: Dissolve in 0.25% Tween 80 and 0.5% Carboxymethyl cellulose Oral Formulation 6: Mixing with food powders Note: Please be aware that the above formulations are for reference only. InvivoChem strongly recommends customers to read literature methods/protocols carefully before determining which formulation you should use for in vivo studies, as different compounds have different solubility properties and have to be formulated differently. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.5097 mL | 12.5483 mL | 25.0966 mL | |
| 5 mM | 0.5019 mL | 2.5097 mL | 5.0193 mL | |
| 10 mM | 0.2510 mL | 1.2548 mL | 2.5097 mL |