1H-Benz[de]isoquinoline-1,3(2H)-dione,2-[2-(dimethylamino)ethyl]-5-nitro-

Names

[ Name ]:
1H-Benz[de]isoquinoline-1,3(2H)-dione,2-[2-(dimethylamino)ethyl]-5-nitro-

[Synonym ]:
2-(2-(dimethylamino)ethyl)-3-nitro-1H-benzo[de]isoquinoline-1,3(2H)-dione
Mitonafidum [INN-Latin]
Mitonafida [INN-Spanish]
M 4212 (Pharmaceutical)
2-(2-(dimethylamino) ethyl)-5-nitro-1H-benzo[de]isoquinoline-1,3(2H)-dione
N-(2-(Dimethylamino)ethyl)-3-nitronaphthalimide
M-4212
2-(2-dimethylaminoethyl)-5-nitrobenzo[de]isoquinoline-1,3-dione
Mitonafide

Biological Activity

[Description]:

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].

[Related Catalog]:

Research Areas >> Cancer

Signaling Pathways >> Cell Cycle/DNA Damage >> DNA/RNA Synthesis

[Target]

DNA and RNA synthesis[1]

[In Vitro]

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.

[In Vivo]

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%.

[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.

Chemical & Physical Properties

[ Density]:
1.384g/cm3

[ Boiling Point ]:
496.8ºC at 760 mmHg

[ Molecular Formula ]:
C₁₆H₁₅N₃O₄

[ Molecular Weight ]:
313.30800

[ Flash Point ]:
254.3ºC

[ Exact Mass ]:
313.10600

[ PSA ]:
88.13000

[ LogP ]:
1.94570

[ Index of Refraction ]:
1.667

[ Storage condition ]:
2-8°C

Toxicological Information

CHEMICAL IDENTIFICATION

RTECS NUMBER :: QK5650000

CHEMICAL NAME :: Naphthalimide, 2-(2-(dimethylamino)ethyl)-5-nitro-

CAS REGISTRY NUMBER :: 54824-17-8

LAST UPDATED :: 199612

DATA ITEMS CITED :: 6

MOLECULAR FORMULA :: C16-H15-N3-O4

MOLECULAR WEIGHT :: 313.34

WISWESSER LINE NOTATION :: T666 1A M CVNVJ D2N1&1 HNW

HEALTH HAZARD DATA

ACUTE TOXICITY DATA

TYPE OF TEST :: LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :: Intraperitoneal

SPECIES OBSERVED :: Rodent - rat

DOSE/DURATION :: 6500 ug/kg

TOXIC EFFECTS :: Tumorigenic - active as anti-cancer agent

TYPE OF TEST :: LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :: Intraperitoneal

SPECIES OBSERVED :: Rodent - mouse

DOSE/DURATION :: 10000 ug/kg

TOXIC EFFECTS :: Tumorigenic - active as anti-cancer agent

MUTATION DATA

TYPE OF TEST :: Mutation test systems - not otherwise specified

TEST SYSTEM :: Rodent - mouse Ascites tumor

DOSE/DURATION :: 4 mg/L

REFERENCE :: CCPHDZ Cancer Chemotherapy and Pharmacology. (Springer-Verlag New York, Inc., Service Center, 44 Hartz Way, Secaucus, NJ 07094) V.1- 1978- Volume(issue)/page/year: 4,61,1980

Safety Information

[ HS Code ]:
2933990090

Precursor & DownStream

Precursor

DownStream

Customs

[ HS Code ]: 2933990090

[ Summary ]:
2933990090. heterocyclic compounds with nitrogen hetero-atom(s) only. VAT:17.0%. Tax rebate rate:13.0%. . MFN tariff:6.5%. General tariff:20.0%

Related Compounds

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