DAMNACANTHAL

中文名称:

DAMNACANTHAL

中文同义词:

3-羟基-1-甲氧基-2-蒽醌甲醛;丹宁卡;丹拿堪索

英文名称:

DAMNACANTHAL

英文同义词:

DAMNACANTHAL;DAMNACANTAL;1-Methoxy-2-formyl-3-hydroxy-9,10-anthraquinone;1-Methoxy-3-hydroxy-9,10-dioxo-9,10-dihydroanthracene-2-carbaldehyde;3-HYDROXY-1-METHOXYANTHRAQUINONE-2-ALDEHYDE;9,10-Dihydroxy-3-hydroxy-1-methoxy-9,10-dioxo-2-anthracenecarboxaldehyde;1-Methoxy-3-hydroxy-9,10-dioxoanthracene-2-carbaldehyde;9,10-Dihydro-3-hydroxy-1-methoxy-9,10-dioxo-2-anthracenecarbaldehyde

CAS号:

477-84-9

分子式:

C16H10O5

分子量:

282.25

EINECS号:

相关类别:

标准品;植物提取物;标准品 -对照药材;其它天然产物

Mol文件:

477-84-9.mol

熔点 

218～219℃

沸点 

531.9±50.0 °C(Predicted)

密度 

1.461±0.06 g/cm3(Predicted)

形态

Pale orange solid.

酸度系数(pKa)

5.26±0.20(Predicted)

CAS 数据库

477-84-9

生物活性

Damnacanthal 是从 Morinda citrifolia 的根中分离出来的蒽醌。Damnacanthal 是一种强效选择性的 p56lck 酪氨酸激酶活性的抑制剂。天然的 Damnacanthal 抑制 p56lck 的自磷酸化和外源底物的磷酸化，IC50 分别为 46 nM 和 220 nM。Damnacanthal 是一种具有抗癌活性的有效凋亡诱导剂。Damnacanthal 在小鼠中也具有镇痛，抗炎作用，并且对白色念珠菌具有抗真菌活性。

靶点

IC50: 46 nM (p56 lck autophosphorylation) and 220 nM (phosphorylation of exogenous substrates by p56 lck ); Apoptosis; Candida albicans

体外研究

Damnacanthal has > 100-fold selectivity for p56 lck over the serine/threonine kinases, protein kinase A and protein kinase C, and > 40-fold selectivity for p56 lck over four receptor tyrosine kinases. Damnacanthal also demonstrates modest (7-20-fold), but highly statistically significant, selectivity for p56 lck over the homologous enzymes p60 src and p59 fyn . Damnacanthal (0.1-100 μM; 1-4 days; HCT-116 and SW480 cells) treatment results in a significant reduction of cell proliferation in a concentration- and time-dependent manner. Damnacanthal (1-50 μM; 72 hours; HCT-116 cells) treatment results in a significant enrichment in the number of cells in the S/G1 and G2/G1 phases at concentration of 50 μM. Damnacanthal (10 μM; 24 hours; HCT-116 cells) treatment significantly increases caspase 3/7 activity. Damnacanthal-induced apoptosis. Damnacanthal (0.1-10 μM; 24 hours; HCT-116 cells) treatment induces NAG-1 expression in HCT-116 cells. Cyclin D1 expression is reduced at 10 μM of Damnacanthal, whereas p21 and p53 does not alter their expression. PARP cleavage is seen at 10 μM Damnacanthal treatment only in HCT-116 cells, where NAG-1 is induced. Damnacanthal treatment for 2 weeks shows significant decreasing colony number in HCT-116 cells in a concentration-dependent manner. Damnacanthal-treated cells show a dramatic inhibition of clonogenic capacity. Damnacanthal-treated (1-50 μM; 48 hours) cells significantly inhibits the migration of HCT-116 cells in a concentration-dependent manner. Cell Proliferation Assay Cell Line: HCT-116 and SW480 cells Concentration: 0.1 μM, 1 μM, 10 μM, 100 μM Incubation Time: 1, 2, and 4 days Result: Resulted in a significant reduction of cell proliferation in a concentration- and time-dependent manner. Cell Cycle Analysis Cell Line: HCT-116 cells Concentration: 1 μM, 10 μM and 50 μM Incubation Time: 72 hours Result: Resulted in a significant enrichment in the number of cells in the S/G1 and G2/G1 phases at concentration of 50 μM. Apoptosis Analysis Cell Line: HCT-116 cells Concentration: 10 μM Incubation Time: 24 hours Result: Significantly increased caspase 3/7 activity. Western Blot Analysis Cell Line: HCT-116 cells Concentration: 0.1 μM, 1 μM and 10 μM Incubation Time: 24 hours Result: NAG-1 was induced in HCT-116 cells in a dose- and time-dependent manner. Cyclin D1 expression was reduced at 10 μM.

Cell Line:

HCT-116 and SW480 cells

Concentration:

0.1 μM, 1 μM, 10 μM, 100 μM

Incubation Time:

1, 2, and 4 days

Result:

Resulted in a significant reduction of cell proliferation in a concentration- and time-dependent manner.

Cell Line:

HCT-116 cells

Concentration:

1 μM, 10 μM and 50 μM

Incubation Time:

72 hours

Result:

Resulted in a significant enrichment in the number of cells in the S/G1 and G2/G1 phases at concentration of 50 μM.

Cell Line:

HCT-116 cells

Concentration:

10 μM

Incubation Time:

24 hours

Result:

Significantly increased caspase 3/7 activity.

Cell Line:

HCT-116 cells

Concentration:

0.1 μM, 1 μM and 10 μM

Incubation Time:

24 hours

Result:

NAG-1 was induced in HCT-116 cells in a dose- and time-dependent manner. Cyclin D1 expression was reduced at 10 μM.

体内研究

Damnacanthal (10-100 mg/kg; oral administration; for 10-300 minutes; male ddY mice) treatment exhibits a significant antinociceptive effect in a dose-dependent manner in the formalin test. Administration of damnacanthal (100 mg/kg) shows significant inhibition of histamine-induced paw edema. Animal Model: Male ddY mice (5-6 weeks) injected with formalin or Histamine Dosage: 10 mg/kg, 30 mg/kg and 100 mg/kg Administration: Oral administration; for 10 minutes, 30 minutes, 60 minutes or 300 minutes Result: Significantly reduced the growth of human lung tumor without acute toxicity.

Animal Model:

Male ddY mice (5-6 weeks) injected with formalin or Histamine

Dosage:

10 mg/kg, 30 mg/kg and 100 mg/kg

Administration:

Oral administration; for 10 minutes, 30 minutes, 60 minutes or 300 minutes

Result:

Significantly reduced the growth of human lung tumor without acute toxicity.