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| Targets |
Mitonafide targets DNA by intercalating into double-stranded DNA, which inhibits DNA and RNA synthesis. It also targets DNA topoisomerase II (TOP2). By intercalating into DNA and inhibiting topoisomerase II, it causes DNA strand breaks and cell cycle arrest. This leads to cytotoxic effects on cancer cells. Its activity against Mycobacterium tuberculosis DNA ligase A suggests additional antimicrobial potential. The compound's naphthalimide core is responsible for its DNA intercalating properties.
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| ln Vitro |
In Chinese hamster ovary cells, mitonafide causes single-strand breaks in DNA and inhibits the synthesis of RNA and DNA [1]. The metabolite 5-aminomitonafide is produced when rat liver microsomes and NADPH are cultured with mitonafide in anaerobic conditions[2]. Single-strand breaks in the DNA of L1210 cells can be induced by mitonafide (25, 50 μM, for one hour) [2]. The HOP-62 lung cell line is cytotoxically affected by mitonafide (10-100 μM) [4].
In vitro, Mitonafide exhibits potent antitumor activity against various cancer cell lines, including breast, lung, and colon cancer. It binds to double-stranded DNA through intercalation and inhibits DNA and RNA synthesis. It is a potent antitumor agent. It also exhibits antiviral activity against herpes simplex virus type 1 and 2. Its effects on cell proliferation and apoptosis can be studied in various cancer cell lines. It is a valuable tool for studying DNA-intercalating agents and topoisomerase II inhibitors. |
| ln Vivo |
In mice carrying S-180, mitonafide (0.5 and 1 mg/kg, i.p., days 1–7) demonstrated antitumor activity [4]. In a HepG2 xenograft model, mierenafide (5 mg/kg, intraperitoneally, twice daily) demonstrated antitumor efficacy [6]. In mice harboring S-180, a single intraperitoneal injection of mitonafide resulted in an LD50 value of 10.0 mg/kg [5].
In vivo, Mitonafide has been studied for its antitumor activity in animal models. It is an investigational compound with potential anti-cancer properties. It has been evaluated in preclinical studies for the treatment of various cancers. However, early clinical trials showed it to be toxic to the central nervous system when administered as a short intravenous infusion. Its ability to intercalate into DNA and inhibit topoisomerase II makes it a promising candidate for cancer therapy, but its CNS toxicity limits its clinical application. |
| Enzyme Assay |
The in vitro DNA intercalation assay for Mitonafide involves measuring its ability to intercalate into DNA using techniques such as DNA melting temperature (Tm) analysis, ethidium bromide displacement assays, or viscometry. The compound's inhibition of DNA and RNA synthesis can be assessed by measuring the incorporation of radiolabeled nucleotides (e.g., [3H]-thymidine, [3H]-uridine) into DNA and RNA in cancer cells. Topoisomerase II inhibition is measured using a DNA relaxation or decatenation assay with purified TOP2.
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| Cell Assay |
Cell viability assay [6]
Cell Types: SK-OV-3, HepG2, A-549, T-24, SMMC-7721, HL-7702 Tested Concentrations: 0-100 μM respectively. Incubation Duration: 48 hrs (hours) Experimental Results: Inhibited cell viability, IC50 values were 6.26, 10.88, 7.94, 5.01, 6.94, 8.51 μM. In vitro cellular assays for Mitonafide use various cancer cell lines, such as NSCLC and leukemia cells. Cells are cultured in appropriate media and treated with the compound at concentrations of 0.1-100 µM for 24-72 hours. Cell viability is assessed using MTT or CCK-8 assays. DNA synthesis is measured by [3H]-thymidine incorporation. Cell cycle analysis is performed by flow cytometry. Apoptosis is evaluated using caspase-3/7 activity assays and Annexin V staining. These assays help characterize its mechanism of action as a DNA intercalator and topoisomerase II inhibitor. |
| Animal Protocol |
Animal/Disease Models: S-180 tumor-bearing mice [4]
Doses: 0.5 mg/kg and 1 mg/kg Route of Administration: intraperitoneal (ip) injection 1-7 days Experimental Results: Median survival time increased. Animal/Disease Models: HepG2 xenograft model [6] Doses: 5 mg/kg Route of Administration: intraperitoneal (ip) injection, twice a day. Experimental Results: The relative tumor growth rate (T/C) value was 28.8%. In vivo animal studies for Mitonafide involve mouse xenograft models using human cancer cell lines. Tumor-bearing mice are treated with the compound via intravenous injection at doses determined from preclinical studies. Tumor volume is measured regularly. The compound's effect on tumor growth is assessed. However, due to its CNS toxicity observed in clinical trials, its in vivo use is limited. The compound is primarily used as a research tool for studying DNA intercalators. |
| ADME/Pharmacokinetics |
Mitonafide is a small molecule with a molecular weight of 313.31 and a molecular formula of C17H11N3O4. It is soluble in DMSO and should be stored at -20°C for long-term preservation. Its pharmacokinetic properties, including half-life and tissue distribution, have been studied in preclinical and clinical settings. It has poor blood-brain barrier penetration, which may contribute to its CNS toxicity. For research use, it can be formulated in suitable vehicles.
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| References |
[1]. Llombart M, et al. Phase I study of mitonafide in solid tumors. Invest New Drugs. 1992 Aug;10(3):177-81.
[2]. inha BK, et al. Mechanism of DNA strand breaks by mitonafide, an imide derivative of 3-nitro-1,8-naphthalic acid. Biochem Pharmacol. 1985 Nov 1;34(21):3845-52. [3]. Rosell R, et al. Phase I study of mitonafide in 120 hour continuous infusion in non-small cell lung cancer. Invest New Drugs. 1992 Aug;10(3):171-5. [4]. Samanta S, et al. Antitumor activity of Nitronaphthal-NU, a novel mixed-function agent. J Exp Ther Oncol. 2005;5(1):15-22. [5]. Pain A, et al. Evaluation of naphthalmustine, a nitrogen mustard derivative of naphthalimide as a rationally-designed anticancer agent. J Exp Clin Cancer Res. 2003 Sep;22(3):411-8. [6]. Xin M, et al. Design, synthesis and biological evaluation of 3-nitro-1,8-naphthalimides as potential antitumor agents. Bioorg Med Chem Lett. 2020 Apr 15;30(8):127051. |
| Additional Infomation |
Mitonafide is a naphthalimide compound with the CAS number 54824-17-8. It intercalates into DNA, inhibits DNA and RNA synthesis, and targets topoisomerase II. It has antitumor activity against NSCLC and leukemia. Early clinical trials showed CNS toxicity. The compound is a research tool and is not for human therapeutic use.
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| Molecular Formula |
C16H15N3O4
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| Molecular Weight |
313.31
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| Exact Mass |
313.106
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| CAS # |
54824-17-8
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| PubChem CID |
327044
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| Appearance |
Light yellow to yellow solid powder
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| Density |
1.384g/cm3
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| Boiling Point |
496.8ºC at 760 mmHg
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| Flash Point |
254.3ºC
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| Index of Refraction |
1.667
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| LogP |
1.945
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| Hydrogen Bond Donor Count |
0
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| Hydrogen Bond Acceptor Count |
5
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| Rotatable Bond Count |
3
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| Heavy Atom Count |
23
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| Complexity |
516
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| Defined Atom Stereocenter Count |
0
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| SMILES |
CN(C)CCN1C(=O)C2=CC=CC3=CC(=CC(=C32)C1=O)[N+](=O)[O-]
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| InChi Key |
XXVLKDRPHSFIIB-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C16H15N3O4/c1-17(2)6-7-18-15(20)12-5-3-4-10-8-11(19(22)23)9-13(14(10)12)16(18)21/h3-5,8-9H,6-7H2,1-2H3
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| Chemical Name |
2-[2-(dimethylamino)ethyl]-5-nitrobenzo[de]isoquinoline-1,3-dione
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| Synonyms |
NSC 300288; NSC-300288; NSC300288
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| HS Tariff Code |
2934.99.9001
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| 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)
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| Solubility (In Vitro) |
DMSO : ~62.5 mg/mL (~199.48 mM)
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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
Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)(e.g. IP/IV/IM/SC) *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). View More
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)] 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). View More
Oral Formulation 3: Dissolved in PEG400 (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 3.1917 mL | 15.9586 mL | 31.9173 mL | |
| 5 mM | 0.6383 mL | 3.1917 mL | 6.3835 mL | |
| 10 mM | 0.3192 mL | 1.5959 mL | 3.1917 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
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