Ellipticine HCl, 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 | C₁₇H₁₅CLN₂ | |
| Molecular Weight | 282.77 | |
| Exact Mass | 282.092 | |
| Elemental Analysis | C, 72.21; H, 5.35; Cl, 12.54; N, 9.91 | |
| CAS # | 5081-48-1 | |
| Related CAS # | Ellipticine;519-23-3 | |
| PubChem CID | 169532 | |
| Appearance | Light yellow to yellow solid powder | |
| LogP | 5.288 | |
| Hydrogen Bond Donor Count | 2 | |
| Hydrogen Bond Acceptor Count | 1 | |
| Rotatable Bond Count | 0 | |
| Heavy Atom Count | 20 | |
| Complexity | 342 | |
| Defined Atom Stereocenter Count | 0 | |
| SMILES | CC1=C(C=NC=C2)C2=C(C)C(N3)=C1C4=C3C=CC=C4.Cl |
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| InChi Key | VSBNVARERCGCEF-UHFFFAOYSA-N | |
| InChi Code | InChI=1S/C17H14N2.ClH/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;1H | |
| Chemical Name | 5,11-dimethyl-6H-pyrido[4,3-b]carbazole;hydrochloride | |
| 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, avoid exposure to moisture. |
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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 | P450; peroxidase; Topo II | ||
| ln Vitro | Ellipticine is a prodrug that damages DNA and is first recognized as a natural product. Its pharmacological efficacy and genotoxic side effects are determined by its 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. Ellipsticine treatment inhibited the growth and proliferation of every tested cell. This effect was linked to the formation of two covalent ellipticine-derived DNA adducts in MCF-7, HL-60, CCRF-CEM, UKF-NB-3, UKF-NB-4, and U87MG cells, but not in neuroblastoma UKF-NB-3 cells. These adducts were identical to those formed by 13-hydroxy- and 12-hydroxyellipticine, the ellipticine metabolites generated by CYP and peroxidase enzymes. 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. | ||
| ln Vivo | Ellipticine treatment causes the DNA of mammary adenocarcinoma and several healthy organs (liver, kidney, lung, spleen, breast, heart, and brain) to produce ellipticine-derived DNA adducts. Compared to normal, healthy mammary tissue, these adenocarcinomas produce nearly twice as many ellipticine-derived DNA adducts. Rats given ellipticine showed increased expression of the cytochrome b5 protein in their livers, indicating that cytochrome b5 might influence the CYP-mediated bioactivation and detoxification of ellipticine. | ||
| 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. |
Solubility Data
| Solubility (In Vitro) |
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 0.84 mg/mL (2.97 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 8.4 mg/mL clear DMSO stock solution to 400 μL of PEG300 and mix evenly; then add 50 μL of Tween-80 to the above solution and mix evenly; then add 450 μL of normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 0.84 mg/mL (2.97 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 8.4 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. 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. Solubility in Formulation 3: ≥ 0.84 mg/mL (2.97 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 8.4 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 3.5364 mL | 17.6822 mL | 35.3644 mL | |
| 5 mM | 0.7073 mL | 3.5364 mL | 7.0729 mL | |
| 10 mM | 0.3536 mL | 1.7682 mL | 3.5364 mL |