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.