Amonafide

Names

[ Name ]:
Amonafide

[Synonym ]:
Amonifide
5-amino-2-[(dimethylamine)ethyl]-1H-benz[de-]isoquinoline-1,3-(2H)-dione
amonafide
1H-Benz[de]isoquinoline-1,3(2H)-dione, 5-amino-2-[2-(dimethylamino)ethyl]-
AS-1413
5-Aminomitonafide
Nafidimide
Benzisoquinolinedione
Quinamed
Amonafidum [Latin]
5-Amino-2-[2-(dimethylamino)ethyl]-1H-benzo[de]isoquinoline-1,3(2H)-dione
2-(2-dimethylaminoethyl)-5-aminobenzo[de]isoquinoline-1,3-dione
5-amino-2-(2-(dimethylamino)ethyl)-1H-benzo[de]isoquinoline-1,3(2H)-dione
Xanafide

Biological Activity

[Description]:

Amonafide is a topoisomerase II inhibitor and DNA intercalator that induces apoptotic signaling by blocking the binding of Topo II to DNA.

[Related Catalog]:

Research Areas >> Cancer

[Target]

Topoisomerase II

[In Vitro]

Amonafide is a topoisomerase II inhibitor and DNA intercalator that induces apoptotic signaling by blocking the binding of Topo II to DNA[1]. Amonafide produces protein-associated DNA cleavage, single-strand breaks (SSB) and DPC and DNA double-strand cleavage. Amonafide (Nafidimide, 400 nM-2.4 μM) reduces the colony-forming ability of the leukemic cell lines in a dose-dependent manner[2]. Amonafide (0.05-0.4 μg/mL) reduces several tumor growth. However, Amonafide is active against only 12% of tumors compared with standard agents (5-fluorouracil, mitomycin C, cisplatin, and etoposide), which are active against more than 40% of tumors in the human bone marrow inhibitory range[3]. Amonafide inhibits the growth of HT-29, HeLa, and PC-3 cell lines, with IC50s of 4.67, 2.73, and 6.38 μM[4].

[Cell Assay]

In experiments measuring survival following 1 h drug treatments, 2 × 106cells are resuspended in 2 mL warm (37°C) HBSS with 5% PCS; the appropriate drug (Amonafide) level is attained with the addition of less than 50 μL. Cells are incubated for 60 min at 37°C after which 10 mL ice cold PBS is added. The cells are then centrifuged at 200 × g for 10 min at 4°C. The wash is repeated once and the cells are resuspended in HBSS with 5% PCS and added to the agar-medium mixture for assessment of surviving clonogenic cells[2].

[References]

[1]. Allen SL, et al. Amonafide: a potential role in treating acute myeloid leukemia. Expert Opin Investig Drugs. 2011 Jul;20(7):995-1003.

[2]. Andersson BS, et al. In vitro toxicity and DNA cleaving capacity of benzisoquinolinedione (nafidimide; NSC 308847) in human leukemia. Cancer Res. 1987 Feb 15;47(4):1040-4.

[3]. Ajani JA, et al. In vitro activity of amonafide against primary human tumors compared with the activity of standard agents. Invest New Drugs. 1988 Jun;6(2):79-85.

[Related Small Molecules]

Chemical & Physical Properties

[ Density]:
1.3±0.1 g/cm3

[ Boiling Point ]:
500.2±35.0 °C at 760 mmHg

[ Melting Point ]:
162-164ºC

[ Molecular Formula ]:
C₁₆H₁₇N₃O₂

[ Molecular Weight ]:
283.325

[ Flash Point ]:
256.3±25.9 °C

[ Exact Mass ]:
283.132080

[ PSA ]:
68.33000

[ LogP ]:
0.06

[ Vapour Pressure ]:
0.0±1.3 mmHg at 25°C

[ Index of Refraction ]:
1.681

[ Storage condition ]:
-20°C Freezer

Toxicological Information

CHEMICAL IDENTIFICATION

RTECS NUMBER :: QK5610000

CHEMICAL NAME :: Naphthalimide, 3-amino-N-(2-(dimethylamino)ethyl)-

CAS REGISTRY NUMBER :: 69408-81-7

LAST UPDATED :: 199612

DATA ITEMS CITED :: 5

MOLECULAR FORMULA :: C16-H17-N3-O2

MOLECULAR WEIGHT :: 283.36

WISWESSER LINE NOTATION :: T666 1A M CVNVT&&J D2N1&1 HZ

HEALTH HAZARD DATA

ACUTE TOXICITY DATA

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

ROUTE OF EXPOSURE :: Intravenous

SPECIES OBSERVED :: Rodent - mouse

DOSE/DURATION :: 67 mg/kg

TOXIC EFFECTS :: Behavioral - changes in motor activity (specific assay) Lungs, Thorax, or Respiration - dyspnea Nutritional and Gross Metabolic - weight loss or decreased weight gain

TYPE OF TEST :: LD - Lethal dose

ROUTE OF EXPOSURE :: Intravenous

SPECIES OBSERVED :: Mammal - dog

DOSE/DURATION :: >18400 ug/kg

TOXIC EFFECTS :: Behavioral - tremor Lungs, Thorax, or Respiration - dyspnea Gastrointestinal - changes in structure or function of salivary glands

MUTATION DATA

TYPE OF TEST :: DNA damage

TEST SYSTEM :: Rodent - mouse Leukocyte

DOSE/DURATION :: 50 umol/L

REFERENCE :: BCPCA6 Biochemical Pharmacology. (Pergamon Press Inc., Maxwell House, Fairview Park, Elmsford, NY 10523) V.1- 1958- Volume(issue)/page/year: 34,3845,1985

Synthetic Route

Click to get detail synthetic route

Precursor & DownStream

Precursor

DownStream

Related Compounds

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