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 在小鼠中也具有抗炎作用，也可用于缓解疼痛的研究，并且对白色念珠菌具有抗真菌活性。
| 生物活性 | Damnacanthal is an anthraquinone isolated from the root ofMorinda citrifolia. Damnacanthal is a highly potent, selective inhibitor ofp56lcktyrosine kinaseactivity. Natural Damnacanthal inhibitsp56lckautophosphorylation and phosphorylation of exogenous substrates withIC50s of 46 nM and 220 nM, respectively. Damnacanthal is a potent inducer ofapoptosiswith anticancer activity. Damnacanthal also has antinociceptive, anti-inflammatory effects in mice and anti-fungal activity againstCandida albicans[1][2][3][4]. |
| IC50& Target | IC50: 46 nM (p56lckautophosphorylation) and 220 nM (phosphorylation of exogenous substrates by p56lck)[1];
Apoptosis[2];
Candida albicans[2] |
体外研究
(In Vitro) | Damnacanthal has >100-fold selectivity for p56lckover the serine/threonine kinases, protein kinase A and protein kinase C, and >40-fold selectivity for p56lckover four receptor tyrosine kinases. Damnacanthal also demonstrates modest (7-20-fold), but highly statistically significant, selectivity for p56lckover the homologous enzymes p60srcand p59fyn[1].
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[2].
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[2].
Damnacanthal (10 μM; 24 hours; HCT-116 cells) treatment significantly increases caspase 3/7 activity. Damnacanthal-induced apoptosis[2].
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[2].
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[2].
Cell Proliferation Assay[2] | 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[2] | 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[2] | Cell Line: | HCT-116 cells | | Concentration: | 10 μM | | Incubation Time: | 24 hours | | Result: | Significantly increased caspase 3/7 activity. |
Western Blot Analysis[2] | 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. |
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体内研究
(In Vivo) | 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[4].
| Animal Model: | Male ddY mice (5-6 weeks) injected with formalin or Histamine[4] | | 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. |
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| 来源 | - Plants
- Rubiaceae
- Morinda citrifoliaLinn.
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| 运输条件 | Room temperature in continental US; may vary elsewhere. |
| 储存方式 | 4°C, protect from light *In solvent : -80°C, 6 months; -20°C, 1 month (protect from light) |
| 溶解性数据 | In Vitro: DMSO : 5 mg/mL(17.71 mM;ultrasonic and warming and heat to 60℃) 配制储备液 | 1 mM | 3.5430 mL | 17.7148 mL | 35.4296 mL | | 5 mM | 0.7086 mL | 3.5430 mL | 7.0859 mL | | 10 mM | 0.3543 mL | 1.7715 mL | 3.5430 mL |
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