Theaflavine-3,3'-digallate，一种具有生物活性的红茶酚类物质，是一种有效的有效的Zika病毒（ZIKV）蛋白酶抑制剂，IC50为2.3μM。
Cas No.:33377-72-9
Sample solution is provided at 25 µL, 10mM.
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Theaflavine-3,3'-digallate is a bioactive tea polyphenol compound. It is an effective inhibitor of the Zika virus (ZIKV) protease with an IC50 of 2.3 μM [1]. Theaflavine-3,3'-digallate directly binds to ZIKVpro (Kd = 8.86μM) and inhibits ZIKV replication. Theaflavine-3,3'-digallate can inhibit the activities of gp41 and NS2B-3 proteases and has antiviral activities against HSV and HIV-1 [2]. Theaflavine-3,3'-digallate is an effective anti-tumor agent and can also be used to study the regulatory effect of intestinal microbiota composition [3].
In vitro, Theaflavine-3,3'-digallate (5-30μM; 3, 72h) pretreatment exhibits growth inhibitory effects on HCT116 cells in a dose- and time-dependent manner, leading to cell cycle arrest and induction of apoptosis, and inhibiting COX-2, iNOS, and ERK1/2 expression [5]. Theaflavine-3,3'-digallate (0-20μM; 6 days) treatment dose-dependently increases the sensitivity of SNU-216 and NCI-N87 cells to trastuzumab (Trast) and reduces cell proliferation [6].
In vivo, Theaflavine-3,3'-digallate (50mg/kg/day; 21 days; i.p.) combined with trastuzumab treatment significantly inhibits tumor growth in xenograft mice carrying NCI-N87 tumor cells and induces a sharp regression of tumors, effectively blocking SHCBP1 nuclear translocation and inhibiting MISP phosphorylation [6].
References:
[1] Cui X, Zhou R, Huang C, et al. Identification of Theaflavin-3,3'-Digallate as a Novel Zika Virus Protease Inhibitor. Front Pharmacol. 2020;11:514313. Published 2020 Oct 21.
[2] Lian Y, Huang Z, Liu X, et al. Discovery of Ten Anti-HIV Hit Compounds and Preliminary Pharmacological Mechanisms Studies[J]. Current HIV Research, 2024, 22(2): 82-90.
[3] Xue Z, Junli Y I N, Jiaxiang W, et al. Research Progress on Anti-Tumor Mechanism of Theaflavins Natural Products[J]. Cancer Research on Prevention and Treatment, 2022, 49(8): 820-826.
[4] Qu F, Liu S, He C, et al. Comparison of the effects of green and black tea extracts on Na+/K+‐ATPase activity in intestine of type 1 and type 2 diabetic mice[J]. Molecular nutrition & food research, 2019, 63(17): 1801039.
[5] Ding Y, Chen B, Gao Z, Suo H, Xiao H. Pre-treated theaflavin-3,3'-digallate has a higher inhibitory effect on the HCT116 cell line. Food Nutr Res. 2017 Nov 15;61(1):1400340.
[6] Shi W, Zhang G, Ma Z, et al. Hyperactivation of HER2-SHCBP1-PLK1 axis promotes tumor cell mitosis and impairs trastuzumab sensitivity to gastric cancer[J]. Nature Communications, 2021, 12(1): 2812.
Theaflavine-3,3'-digallate，一种具有生物活性的红茶酚类物质，是一种有效的有效的Zika病毒（ZIKV）蛋白酶抑制剂，IC50为2.3μM [1]。Theaflavin 3,3'-digallate直接与ZIKVpro结合（Kd=8.86μM）并抑制ZIKV复制。Theaflavine-3,3'-digallate能够抑制gp41和NS2B-3蛋白酶的活性，并具有抗HSV和HIV-1病毒活性 [2]。Theaflavine-3,3'-digallate是一种有效的抗肿瘤剂，也可用于研究肠道菌群组成调节作用 [3]。
在体外，Theaflavine-3,3'-digallate（5-30μM; 3, 72h）预处理以剂量和时间依赖性的方式对HCT116细胞发挥生长抑制作用，导致细胞周期停滞和诱导细胞凋亡，并抑制COX-2，iNOS和ERK1/2的表达[5]。Theaflavine-3,3'-digallate（0-20μM; 6 days）处理剂量依赖性增加了SNU-216和NCI-N87细胞对曲妥珠单抗（Trast）的敏感性并减少细胞增殖 [6]。
在体内，Theaflavine-3,3'-digallate（50mg/kg/day; 21days; i.p. ）与曲妥珠单抗联合治疗显著抑制了携带NCI-N87肿瘤细胞的异种移植小鼠的肿瘤生长并诱导了肿瘤的急剧消退，有效阻断了SHCBP1核易位并抑制MISP磷酸化 [6]。
| Kinase experiment [1]: | |
Preparation Method | Mixtures of Na+/K+-ATPase enzyme, Tris-buffer (containing 1mM ouabain or not), and different concentrations of Theaflavine-3,3’-digallate were preincubated at 37°C as the method of the Na+/K+-ATPase activity assay. Increasing concentrations of the substrate ATP in the range of 2.0–5.0mM were added to estimate the ATP kinetics of Na+/K+-ATPase. After incubation for 60min at 37°C, 200µL of trichloroacetic acid was added to terminate the reaction, and the liberated inorganic phosphorus was determined by a phosphate assay kit. The Vmax and Km constants were determined using Lineweaver–Burk plots generated from the relevant Michaelis–Menten equations. The Na+/K+-ATPase kinetics for the Na+ or K+ cofactors were determined by the same method in the presence of increasing concentrations of NaCl or KCl in the range of 1.0–8.0mM or 0.5–4.0mM. The amount of ATP was constant (5mM). |
Reaction Conditions | 0-30μM; 60min |
Applications | Theaflavine-3,3’-digallate significantly inhibits Na+/K+-ATPase activity in a dose-dependent manner. |
| Cell experiment [2]: | |
Cell lines | HCT116 cells |
Preparation Method | Cell viability was assessed using a variation of the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenytetrazolium bromide (MTT) assay. HCT116 cells were seeded into 96-well plates (2×103 cells/well). After 24h of incubation at 37°C, the cells were treated with four conditions of Theaflavine-3,3’-digallate (TFDG). First, the cells were treated with different concentrations of TFDG (TFDG, 5–30μM) for 72h. Second, the cells were treated with different concentrations of pre-treated TFDG (O-TFDG) for 72h. The concentration of O-TFDG was expressed in TFDG equivalents. Third, the cells were treated by TFDG for only 3h, after which the media were replaced by fresh media for another 69h incubation (TFDG-3). Fourth, the cells were treated by O-TFDG for only 3h, after which the media were replaced by fresh media for another 69h of incubation (O-TFDG-3). After 72h, the number of viable cells compared with the control were detected using MTT assay. The treatment media were changed with 100μl of fresh media containing 0.5mg/ml of MTT and incubated for 1.5h. The media were replaced again by 100μl of DMSO. After gentle shaking, the optical density (OD) was measured at 570nm using a microplate reader. |
Reaction Conditions | 5-30μM; 3, 72h |
Applications | The Theaflavine-3,3’-digallate pretreatment exerts growth inhibitory effects on HCT116 cells in a dose- and time-dependent manner. |
| Animal experiment [3]: | |
Animal models | BALB/c nude mice (NCI-N87/luc tumor xenograft models) |
Preparation Method | NCI-N87/luc tumor xenograft models were established in athymic nude mice. Tumors were imaged by an in vivo Imaging System. To evaluate SHCBP1 knockdown involving in the gastric cancer sensitivity to trastuzumab, female BALB/c nude mice (6–8 weeks of age) received single subcutaneous flank injection of 1 × 106 Lenti-vector or Lenti-shRNA targeting NCI-N87/luc cells in a 1:1 PBS:Matrigel suspension. When tumor volumes reached 100mm3, trastuzumab was given at 10mg/kg intraperitoneally twice weekly. Tumors were measured by caliper three times per week. Animals were sacrificed and immunohistochemical staining was performed in the tumors after drug treatment for 21 days. To determine the synergistic effects of combining trastuzumab with Theaflavine-3,3'-digallate, NCI-N87/luc cells (1 × 106 cells per site) in suspension were mixed with equal volumes of Matrigel and injected subcutaneously into 6–8-week old female BALB/c nude mice. When tumor volumes reached 100mm3, preestablished NCI-N87 tumor xenografts were treated with vehicle, trastuzumab (intraperitoneal, 10mg/kg, 2×/wk × 3), Theaflavine-3,3'-digallate (subcutaneous, 2.5mg/kg or intraperitoneal, 50mg/kg, 1×/day × 21), or a combination of the agents. At the end of experiments, animals were sacrificed and subcutaneous tumors were harvested. Tumor proliferation was assessed by Ki-67 immunohistochemical staining. |
Dosage form | 50mg/kg/day; 21 days; i.p. |
Applications | Theaflavine-3,3'-digallate combined with trastuzumab treatment significantly inhibited the tumor growth in xenograft mice carrying NCI-N87 tumor cells and induced a sharp regression of the tumors. |
References: | |
| Cas No. | 33377-72-9 | SDF | |
| 别名 | 茶黄素-3,3'-双没食子酸(TFBG) | ||
| 化学名 | (2S,3S)-2-(8-((2R,3R)-5,7-dihydroxy-3-((3,4,5-trihydroxybenzoyl)oxy)chroman-2-yl)-3,4,6-trihydroxy-5-oxo-5H-benzo[7]annulen-1-yl)-5,7-dihydroxychroman-3-yl 3,4,5-trihydroxybenzoate | ||
| Canonical SMILES | OC(C=C1O2)=CC(O)=C1C[C@](OC(C3=CC(O)=C(O)C(O)=C3)=O)([H])[C@@]2([H])C(C=C4O)=CC(C([C@@]5([H])[C@](OC(C6=CC(O)=C(O)C(O)=C6)=O)([H])CC7=C(O)C=C(O)C=C7O5)=CC(O)=C8O)=C8C4=O | ||
| 分子式 | C43H32O20 | 分子量 | 868.7 |
| 溶解度 | Soluble in DMSO | 储存条件 | Store at -20°C |
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| 制备储备液 | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 1.1511 mL | 5.7557 mL | 11.5115 mL |
| 5 mM | 230.2 μL | 1.1511 mL | 2.3023 mL |
| 10 mM | 115.1 μL | 575.6 μL | 1.1511 mL |
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动物平均体重 | g | |
每只动物给药体积 | ul | |
动物数量 | 只 |
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| % DMSO % % Tween 80 % saline | ||||||||||
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工作液浓度： mg/ml；
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2.
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