Ellipticine, originally identified as a natural product, is a DNA-damaging agent acting as a prodrug whose pharmacological efficiencies and genotoxic side effects are dictated by activation with cytochrome P450 (CYP). With several modes of action, including DNA intercalation and inhibition of DNA topoisomerase II, ellipticine is a highly effective antitumor agent. In addition to its pharmacological and genotoxic effects, ellipticine can also be used as an inducer or inhibitor of biotransformation enzymes, which can alter its own metabolism. Cell growth and proliferation were inhibited when ellipticine was administered to all tested cells. This effect was linked, in MCF-7, HL-60, CCRF-CEM, UKF-NB-3, UKF-NB-4, and U87MG cells, to the formation of two covalent ellipticine-derived DNA adducts, which were identical to those formed by 13-hydroxy- and 12-hydroxyellipticine, the ellipticine metabolites generated by CYP and peroxidase enzymes, but not in neuroblastoma UKF-NB-3 cells. Consequently, the majority of cancer cell lines examined in this comparative study may be more sensitive to ellipticine treatment due to DNA adduct formation, while other ellipticine action mechanisms may also play a role in the drug's cytotoxicity against neuroblastoma UKF-NB-3 cells.
Physicochemical Properties
| Molecular Formula | C17H14N2 | |
| Molecular Weight | 246.31 | |
| Exact Mass | 246.115 | |
| Elemental Analysis | C, 82.90; H, 5.73; N, 11.37 | |
| CAS # | 519-23-3 | |
| Related CAS # | Ellipticine hydrochloride;5081-48-1 | |
| PubChem CID | 3213 | |
| Appearance | Yellow solid powder | |
| Density | 1.3±0.1 g/cm3 | |
| Boiling Point | 495.4±40.0 °C at 760 mmHg | |
| Melting Point | 316-318°C | |
| Flash Point | 227.1±18.6 °C | |
| Vapour Pressure | 0.0±1.2 mmHg at 25°C | |
| Index of Refraction | 1.777 | |
| LogP | 4.8 | |
| Hydrogen Bond Donor Count | 1 | |
| Hydrogen Bond Acceptor Count | 1 | |
| Rotatable Bond Count | 0 | |
| Heavy Atom Count | 19 | |
| Complexity | 342 | |
| Defined Atom Stereocenter Count | 0 | |
| SMILES | CC1=C(C=NC=C2)C2=C(C)C(N3)=C1C4=C3C=CC=C4 |
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| InChi Key | CTSPAMFJBXKSOY-UHFFFAOYSA-N | |
| InChi Code | InChI=1S/C17H14N2/c1-10-14-9-18-8-7-12(14)11(2)17-16(10)13-5-3-4-6-15(13)19-17/h3-9,19H,1-2H3 | |
| Chemical Name | 5,11-dimethyl-6H-pyrido[4,3-b]carbazole | |
| Synonyms |
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| 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 Note: Please store this product in a sealed and protected environment (e.g. under nitrogen), avoid exposure to moisture and light. |
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| 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 | Ellipticine (NSC 71795) is a strong anti-tumor agent that acts through multiple modes of action. Ellipticine (NSC 71795) is thought to exert its antitumor, mutagenic, and cytotoxic properties through the mechanisms of intercalation into DNA and inhibition of DNA topoisomerase II activity. Ellipticine (NSC 71795) also acts through oxidizing DNA with cytochromes P450 (CYP) and peroxidases, which forms covalent DNA adducts[1]. Ellipticine (NSC 71795) has pharmacological and genotoxic effects because it can also modulate its own metabolism by acting as an inducer or inhibitor of biotransformation enzymes. The application of Ellipticine (NSC 71795) to cells inhibits their growth and proliferation. Two covalent DNA adducts derived from ellipticine (NSC 71795) are linked to this effect[2]. | ||
| ln Vivo | Ellipticine (NSC 71795) treatment causes the DNA of mammary adenocarcinoma and several healthy organs (liver, kidney, lung, spleen, breast, heart, and brain) to produce adducts of Ellipticine (NSC 71795). These adenocarcinomas produce nearly twice as much Ellipticine (NSC 71795)-derived DNA adducts than do normal, healthy mammary tissue. Cytochrome b5 may influence CYP-mediated bioactivation and detoxification of ellipticine (NSC 71795), as evidenced by the induced expression of cytochrome b5 protein in the liver of rats treated with the drug[3]. | ||
| Enzyme Assay | Ellipticine is a strong antitumor agent that acts through multiple modes of action. The mechanisms underlying the cytotoxic, mutagenic, and antitumor properties of ellipticine are proposed to involve DNA intercalation and inhibition of DNA topoisomerase II activity. The oxidation of DNA with cytochromes P450 (CYP) and peroxidases results in the formation of covalent DNA adducts, which is another way that ellipticine acts[1]. Ellipticine's pharmacological and genotoxic effects result from its ability to modulate its own metabolism through the inhibition or induction of biotransformation enzymes. The application of ellipticine to cells inhibits their growth and proliferation. Two covalent DNA adducts derived from ellipticines are linked to this effect. | ||
| Cell Assay | The MTT test is used to evaluate the cytotoxicity of ellipticine (NSC 71795). To get final concentrations of 0, 0.1, 1, 5, or 10 μM, ellipticine (NSC 71795) is diluted in culture medium after being dissolved in DMSO (1 mM). In a 96-well microplate, 1×104 cells are seeded per well for exponential growth. Following four hours of incubation, the MTT solution is added, and the cells are lysed in 50% N,N-dimethylformamide with 20% sodium dodecyl sulfate (SDS) at a pH of 4.5. At 570 nm, the absorbance is measured. As a background, the mean absorbance of the medium controls is subtracted. The values of treated cells are computed as a percentage of control, with the viability of control cells being assumed to be 100%. The dose-log response curves are linearly regressed to determine the IC50 values[2]. | ||
| Animal Protocol |
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| References |
[1]. Molecular mechanisms of antineoplastic action of an anticancer drug ellipticine. Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub. 2006 Jul;150(1):13-23. [2]. Ellipticine cytotoxicity to cancer cell lines - a comparative study. Interdiscip Toxicol. 2011 Jun;4(2):98-105. [3]. The anticancer drug ellipticine activated with cytochrome P450 mediates DNA damage determining its pharmacological efficiencies: studies with rats, Hepatic Cytochrome P450 Reductase Null (HRN?) mice and pure enzymes. Int J Mol Sci. 2014 Dec 25;16(1):284-306. |
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| Additional Infomation |
Ellipticine is a organic heterotetracyclic compound that is pyrido[4,3-b]carbazole carrying two methyl substituents at positions 5 and 11. It has a role as an antineoplastic agent and a plant metabolite. It is an organic heterotetracyclic compound, an organonitrogen heterocyclic compound, a polycyclic heteroarene and an indole alkaloid. Ellipticine is a potent antineoplastic agent. Ellipticine has been reported in Trichoderma brevicompactum, Aschersonia paraphysata, and other organisms with data available. |
Solubility Data
| Solubility (In Vitro) |
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| 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 | 4.0599 mL | 20.2996 mL | 40.5992 mL | |
| 5 mM | 0.8120 mL | 4.0599 mL | 8.1198 mL | |
| 10 mM | 0.4060 mL | 2.0300 mL | 4.0599 mL |