Mitonafide
(Synonyms: NSC 300288) 目录号 : GC67716Mitonafide (NSC 300288) 是一种细胞生长抑制剂。Mitonafide 通过嵌入 DNA 而与双链 DNA 结合，抑制 DNA 和 RNA 的合成。Mitonafide 是一种抗肿瘤剂，可用于癌症研究，如非小细胞肺癌 (NSCLC)、白血病。
Cas No.:54824-17-8
Sample solution is provided at 25 µL, 10mM.
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Quality Control & SDS
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- Purity: >99.00%
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- SDS (Safety Data Sheet)
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Mitonafide (NSC 300288) is a cytostatic agent. Mitonafide binds to double-stranded DNA through intercalation, and inhibits DNA and RNA synthesis. Mitonafide is an antitumor agent that can be used in the research of cancers, such as non-small cell lung cancer (NSCLC), leukemia[1][2][3].
Mitonafide inhibits DNA and RNA synthesis and induces single-strand breaks in the DNA of chinese hamster ovary cells[1].
The incubation of Mitonafide with rat liver microsomes and NADPH under anaerobic conditions results in the formation of a metabolite identified as 5-aminomitonafide[2].
Mitonafide (25, 50 μM, 1 h) induces single-stand breaks in the DNA of L1210 cells[2].
Mitonafide (10-100 μM) exhibits cytotoxic effect in the HOP-62 lung cell line[4].
Cell Viability Assay[6]
| Cell Line: | SK-OV-3, HepG2, A-549, T-24, SMMC-7721, HL-7702 |
| Concentration: | 0-100 μM respectively. |
| Incubation Time: | 48 h |
| Result: | Inhibited cell viability with IC50 values of 6.26, 10.88, 7.94, 5.01, 6.94, 8.51 μM. |
Mitonafide (0.5 and 1 mg/kg, i.p., 1-7 days) shows antitumoral potency in S-180 bearing mice[4].
Mitonafide (5 mg/kg, i.p., twice a day) shows anticancer activity in HepG2 xenograft model[6].
Mitonafide (single i.p. injection, S-180 bearing mice) shows the LD50 value of 10.0 mg/kg[5].
| Animal Model: | S-180 bearing mice[4] |
| Dosage: | 0.5 mg/kg and 1 mg/kg |
| Administration: | Intraperitoneal injection (i.p.) for 1-7 days |
| Result: | Increased in median survival times. |
| Animal Model: | HepG2 xenograft model [6] |
| Dosage: | 5 mg/kg |
| Administration: | Intraperitoneal injection (i.p.), twice a day. |
| Result: | Exhibited a relative tumor increment rates (T/C) value of 28.8%. |
[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.
| Cas No. | 54824-17-8 | SDF | Download SDF |
| 别名 | NSC 300288 | ||
| 分子式 | C16H15N3O4 | 分子量 | 313.31 |
| 溶解度 | DMSO : 62.5 mg/mL (199.48 mM; Need ultrasonic) | 储存条件 | Store at -20°C |
| General tips | 请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。 储备液的保存方式和期限：-80°C 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。 为了提高溶解度，请将管子加热至37℃，然后在超声波浴中震荡一段时间。 |
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| Shipping Condition | 评估样品解决方案：配备蓝冰进行发货。所有其他可用尺寸：配备RT，或根据请求配备蓝冰。 | ||
| 制备储备液 | |||
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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 |
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动物平均体重 | g | |
每只动物给药体积 | ul | |
动物数量 | 只 |
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工作液浓度： mg/ml；
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2.
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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.PMID:4062959DOI:10.1016/0006-2952(85)90433-2.
The metabolism and the mechanism of action of 5-nitro-2-(2-dimethylaminoethyl)-benzo(de) isoquinoline-1,3-dione (Mitonafide), a nitro-containing antitumor drug, have been studied. Incubation of Mitonafide under anaerobic conditions with rat liver microsomes and NADPH formed the fully reduced amine metabolite, 5-aminomitonafide. The formation of the amine metabolite was not inhibited by SKF-525A, metyrapone or piperonyl butoxide, indicating that the cytochrome P-450 was not involved in this reduction. Incubation of Mitonafide with rat liver microsomes and NADPH under aerobic conditions stimulated oxygen consumption; piperonyl butoxide, SKF-525A, superoxide dismutase and catalase had no effect on this stimulation. Both Mitonafide and 5-aminomitonafide were found to bind to DNA in a similar manner. However, in inducing single-stand breaks in the DNA of L1210 cells Mitonafide was 10-fold more potent than 5-aminomitonafide. These results suggest that metabolic activation of Mitonafide to species other than that of the amine metabolite may play a significant role in the induction of DNA damage and the biological activity of the drug.
Phase II study of Mitonafide in advanced and relapsed colorectal cancer
Invest New Drugs 1996;14(2):223-5.PMID:8913845DOI:10.1007/BF00210795.
Background: This study investigated the antitumoral activity in colorectal cancer and toxicity of a 5-day continuous infusion of a new cytostatic agent, Mitonafide, that had previously shown to be neurotoxic when administered as a short daily x 5 days infusion. Patients and methods: Seventeen chemotherapy-naive patients with advanced or relapsed colorectal cancer and measurable disease entered the study. All but one received a 120-hour (5-day) continuous infusion of Mitonafide at a starting dose of 200 mg/m2/day every 3 weeks. Toxicity evaluation was performed after each course and response assessment every 2 courses using the standard World Health Organization (WHO) criteria completed by the "Mini-mental state" test for cognitive status examination. Results: Sixteen patients received a total of 41 courses of Mitonafide which resulted to be severely myelotoxic. In total, 13/16 patients had WHO grade 3-4 neutropenia, 7 of them with infection, and the treatment had to be stopped in 3 patients after only 1 course due to excessive toxicity. No central nervous system toxicity was observed. No objective responses were evidenced. Conclusions: At the dose and schedule of administration used, Mitonafide is not active in colorectal cancer and induces severe myelotoxicity thus not deserving further studies in this indication.
Effect of Mitonafide analogs on topoisomerase II of Leishmania chagasi
Antimicrob Agents Chemother 1996 Mar;40(3):706-9.PMID:8851597DOI:10.1128/AAC.40.3.706.
Mitonafide (4-nitro-benzoisoquinolinedione) and a number of structural analogs were synthesized and studied in order to determine the structural requirements for inhibition of leishmanial nuclear and kinetoplast topoisomerase II and human topoisomerase II. The structure-activity relationship studies with the Mitonafide analogs demonstrated that there was selective targeting of leishmanial nuclear topoisomerase II and human topoisomerase II and differential targeting of kinetoplast over nuclear topoisomerase II in the parasite. Mitonafide analogs appeared to have multiple mechanisms of action leading to death of leishmanias, but several compounds that affected kinetoplast but not nuclear topoisomerase II were not cytotoxic as determined by short-term assays. These studies provide new insight into the differential sensitivities of leishmanial nuclear and kinetoplast topoisomerase II to topoisomerase II-targeting drugs.
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.PMID:1330970DOI:10.1007/BF00877242.
Mitonafide is the lead compound of a new series of antitumor drugs, the 3-Nitronaphthalimides, which have shown antineoplastic activity in vitro as well as in vivo. This phase I Mitonafide study in non-small cell lung cancer using a 120-hour continuous infusion (120 h. C.I.) schedule of administration was designed to deliver the maximum amount of drug while avoiding the risk of central nervous system (CNS) toxicity, previously observed in studies with daily short (1 hour) administration schedules. Twenty patients were treated at doses ranging from 107-200 mg/m2 x 120 h. C.I. Dose-limiting toxicity with this schedule of administration was leukopenia. Other toxicities were mild or not relevant. No CNS toxicity was observed. The recommended dose for phase II C.I. Mitonafide studies is 170 mg/m2 x 120 h. C.I. in previously untreated patients. Plasma level monitoring is recommended.
Design, synthesis, and biological evaluation of new Mitonafide derivatives as potential antitumor drugs
Bioorg Med Chem 2008 Sep 15;16(18):8440-6.PMID:18774722DOI:10.1016/j.bmc.2008.08.027.
A series of potential DNA-binding antitumor agents, 2-[omega-(alkylamino)alkyl]-6-{[omega-(alkylamino)alkyl]amino}-1H-benzo[de]isoquinolin-1,3(2H)-diones and 1,7-bis{6-[(omega-(dimethylamino)alkyl)amino]-1,3-dioxo-1H-benzo[de]isoquinolin-2(3H)-yl}-4-methyl-4-azaheptanes, have been prepared as Mitonafide derivatives. Their DNA-binding ability and cytotoxic activity have been evaluated. Some of the target compounds have shown high DNA affinity as well as relevant cytotoxic properties.