11-amino-3-[2-(dimethylamino)ethyl]-3-azatricyclo[7.3.1.05,13]trideca-1(13),5,7,9,11-pentaene-2,4-dione

• ChemBase编号: 72640
• 分子式: C16H17N3O2
• 平均质量: 283.32508
• 单一同位素质量: 283.1320768
• SMILES: c12cc(cc3c1c(ccc2)c(=O)n(c3=O)CCN(C)C)N
• Canonical SMILES: CN(CCn1c(=O)c2cc(N)cc3c2c(c1=O)ccc3)C
• InChI: InChI=1S/C16H17N3O2/c1-18(2)6-7-19-15(20)12-5-3-4-10-8-11(17)9-13(14(10)12)16(19)21/h3-5,8-9H,6-7,17H2,1-2H3
• InChIKey: UPALIKSFLSVKIS-UHFFFAOYSA-N

名称和登记号

名称

• IUPAC标准名: 11-amino-3-[2-(dimethylamino)ethyl]-3-azatricyclo[7.3.1.0^5,^1^3]trideca-1(13),5,7,9,11-pentaene-2,4-dione; 11-amino-3-[2-(dimethylamino)ethyl]-3-azatricyclo[7.3.1.0^{5,13}]trideca-1(13),5,7,9,11-pentaene-2,4-dione
• IUPAC传统名: amonafide
• 别名: 5-Amino-2-[2-(dimethylamino)ethyl]-1H-benz[de]isoquinoline-1,3(2H)-dione; FA 142; M-FA 142; MADE-FA 142; NCI 308847; NSC 308847; Nafidimide; AS1413; Xanafide; Quinamed; Amonafide

登记号

• CAS号: 69408-81-7
• PubChem SID: 162037565
• PubChem CID: 50515

理论计算性质

• 质子受体: 4
• 质子供体: 1
• LogD (pH = 5.5): -1.7992526
• LogD (pH = 7.4): -0.05132785
• Log P: 1.0962944
• 摩尔折射率: 83.3812 cm^3
• 极化性: 31.664867 Å^3
• 极化表面积: 66.64 Å^2
• 可自由旋转的化学键: 3
• 里宾斯基五规则: true

分子性质

理化性质

• 溶解度: DMSO; Methanol
• 外观: Brownish Yellow Solid
• 熔点: 162-164°C

安全信息

• 保存条件: -20°C; -20°C Freezer

药理学性质

• 作用靶点: topoisomerase

产品相关信息

• 成盐信息: Free Base

详细说明

Selleck Chemicals - S1367

Research Area

• Description: Prostate cancer,Ovarian cancer,Breast cancer

Biological Activity

• Description: Amonafide (NSC-308847) is a selective topoisomerase II inhibitor.
• Targets: Topoisomerase II
• In Vitro: Through a topoisomerase II-mediated reaction, Amonafide treatment produces DNA single-strand breaks (SSB), double-strand breaks (DSB), and DNA-protein cross-links in human myeloid leukemia cells. Amonafide treatment inhibits conlony formation of the leukemic cell lines and the normal human bone marrow GM-CFC in a dose-dependent manner. Amonafide does not produce topoisomerase I-mediated DNA cleavage even at 100 μM. The m-AMSA-resistant line is less than 2-fold resistant to Amonafide ^[1] Amonafide interferes with the DNA breakage-reunion activity of mammalian DNA topoisomerase II resulting in DNA cleavage stimulation. ^[2] Compared with those of other antitumor drugs, Amonafide-stimulated cleavage intensity patterns are markedly different. Amonafide highly prefers a cytosine, and excludes guanines and thymines instead, at position -1, with lower preference for an adenine at position +1. ^[3] Topoisomerase II-mediated DNA cleavage induced by Amonafide is affected only slightly (less than 3-fold) by 1 mM ATP, suggeting that Amonafide is an ATP-insensitive topoisomerase II inhibitor in contrast to doxorubicin, etoposide, and mitoxantrone. ^[4] Amonafide significantly inhibits the growth of HT-29, HeLa, and PC3 cells with IC50 of 4.67 μM, 2.73 μM, and 6.38 μM, respectively. ^[5] Amonafide is unaffected by P-glycoprotein-mediated efflux, unlike those of the classical topoisomerase II inhibitors (daunorubicin, doxorubicin, idarubicin, etoposide, and mitoxantrone). ^[6]
• Clinical Trials: A Phase I/II study of Amonafide in men with androgen-independent prostate cancer has been completed.

Protocol

• Protocol: Cell Assay ^[5]
• Cell Lines: HT-29, HeLa, and PC3
• Concentrations: Dissolved in DMSO, final concentrations ~10 μM
• Incubation Time: 72 hours
• Methods: All cell lines are in the logarithmic phase of growth when the assay of 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) is carried out. Cells are harvested and seeded into 96-well tissue culture plates at a density of 2.5 × 10^3 cells/well in 150 μL aliquots of medium. The concentrations tested are serial dilutions of a stock solution (10 μM in DMSO) with phosphate-buffered saline (PBS) and are added 24 hours later. The assay is ended after 72 hours of Amonafide exposure and PBS is used as a negative control. After 72 hours treatment, cells are washed twice with PBS, and then 50 μL/well of MTT reagent (1 mg/mL in PBS) together with 150 μL/well of prewarmed medium are added. The plates are returned to the incubator for 4 hours. Subsequently, DMSO is added as solvent. Absorbance is determined at 570 nm with a Microplate reader. All experiments were performed at least three times, and the average of the percentage absorbance is plotted against concentration. Then, the concentration of Amonafide required to inhibit 50% of cell growth (IC50) is calculated for Amonafide.

References

• References: [1] Andersson BS, et al. Cancer Res, 1987, 47(4), 1040-1044.
• References: [2] Hsiang YH, et al. Mol Pharmacol, 1989, 36(3), 371-376.
• References: [3] De Isabella P, Nucleic Acids Res, 1995, 23(2), 223-229.
• References: [4] Wang H, et al. J Biol Chem, 2001, 276(19), 15990-15995.
• References: [5] Braña MF, et al. J Med Chem, 2004, 47(6), 1391-1399.
• References: [6] Chau M, et al. Leuk Res, 2008, 32(3), 465-473.

Toronto Research Chemicals - A634205

Amonafide is a DNA intercalator and topoisomerase II inhibitor in clinical development for the treatment of neoplastic diseases. Antitumor agent.

参考文献

• Andersson BS, et al. Cancer Res, 1987, 47(4), 1040-1044.
• Hsiang YH, et al. Mol Pharmacol, 1989, 36(3), 371-376.
• De Isabella P, Nucleic Acids Res, 1995, 23(2), 223-229.
• Wang H, et al. J Biol Chem, 2001, 276(19), 15990-15995.
• Braña MF, et al. J Med Chem, 2004, 47(6), 1391-1399.
• Chau M, et al. Leuk Res, 2008, 32(3), 465-473.
• Hsiang, Y., et al.: Mol. Pharmacol., 36, 371 (1989)
• Costanza, M., et al.: Clin. Cancer Res., 1, 699 (1989)
• Innocenti, F., et al.: Drug Metab. Dispos., 29, 596 (1989)
• Brana, M., et al.: J. Med. Chem., 47, 1391 (1989)