Episilvestrol
目录号 : GC35998
Episilvestrol 是 silvestrol 的衍生物，从 Aglaia silvestris 中分到，能够抑制 eIF4A 靶作用的转录过程。
Cas No.:697235-39-5
Sample solution is provided at 25 µL, 10mM.
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Quality Control & SDS
- View current batch:
- Purity: >99.50%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Cell experiment: | A total of 1×104 HK1 cells/well or 3×104 C666.1 cells/well are seeded into 96-multiwell microtiter plates. At 24 h following seeding, the medium is aspirated and replaced with fresh medium containing various concentrations of silvestrol or Episilvestrol. Vehicle control cultures receive DMSO alone. The cells are then incubated for 24 h at 37°C in an atmosphere containing 5% CO2. The number of viable cells at the end of the incubation period is measured using MTS assay. Absorbance at 490 nm is read and subtracted with non-specific absorbance measured at 630 nm. Wells containing medium without cells serve as blanks. Cell viability is calculated as a percentage compared to the control cells, which are arbitrarily assigned 100% viability. The half maximal inhibitory concentration (IC50) values are graphically obtained from the dose-response curves[3]. |
References: [1]. Chambers JM, et al. Synthesis of biotinylated episilvestrol: highly selective targeting of the translation factors eIF4AI/II. Org Lett. 2013 Mar 15;15(6):1406-9. | |
Episilvestrol is a derivative of silvestrol, isolated from the fruits and twigs of Aglaia silvestris, and is a specific eIF4A-targeting translation inhibitor, with antitumor activity. eIF4A[1]
Episilvestrol is a specific eIF4A-targeting translation inhibitor, with antitumor activity[1]. Episilvestrol is cytotoxic activity against several human cancer cell lines, such as Lu1, LNCaP, MCF-7 and HUVEC cells, with ED50s of 3.8, 3.8, 5.5 and 15.3 nM, respectively[2]. The GI50s of Episilvestrol against the cell proliferation of NCI-H460 and MCF-7 cels are 17.96 nM and 17.96 nM after first test and 15.6 nM and 18.7 nM after 2 months via SRB assay. Episilvestrol also suppresses HK1 cells and EBV-positive C666.1 NPC cells[3].
[1]. Chambers JM, et al. Synthesis of biotinylated episilvestrol: highly selective targeting of the translation factors eIF4AI/II. Org Lett. 2013 Mar 15;15(6):1406-9. [2]. Hwang BY, et al. Silvestrol and episilvestrol, potential anticancer rocaglate derivatives from Aglaia silvestris. J Org Chem. 2004 May 14;69(10):3350-8. [3]. Daker M, et al. Inhibition of nasopharyngeal carcinoma cell proliferation and synergism of cisplatin with silvestrol and episilvestrol isolated from Aglaia stellatopilosa. Exp Ther Med. 2016 Jun;11(6):2117-2126. Epub 2016 Mar 29.
| Cas No. | 697235-39-5 | SDF | |
| Canonical SMILES | O=C([C@H]([C@H]1C2=CC=CC=C2)[C@@H](O)[C@]3(O)[C@@]1(C4=CC=C(OC)C=C4)OC5=CC(O[C@@H]6O[C@@H]([C@@H](O)CO)CO[C@H]6OC)=CC(OC)=C35)OC | ||
| 分子式 | C34H38O13 | 分子量 | 654.66 |
| 溶解度 | Soluble in DMSO | 储存条件 | Store at -20°C |
| General tips | 请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。 储备液的保存方式和期限：-80°C 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。 为了提高溶解度，请将管子加热至37℃，然后在超声波浴中震荡一段时间。 |
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| Shipping Condition | 评估样品解决方案：配备蓝冰进行发货。所有其他可用尺寸：配备RT，或根据请求配备蓝冰。 | ||
| 制备储备液 | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 1.5275 mL | 7.6376 mL | 15.2751 mL |
| 5 mM | 0.3055 mL | 1.5275 mL | 3.055 mL |
| 10 mM | 0.1528 mL | 0.7638 mL | 1.5275 mL |
| 第一步：请输入基本实验信息（考虑到实验过程中的损耗，建议多配一只动物的药量） | ||||||||||
| 给药剂量 | mg/kg |  |
动物平均体重 | g | |
每只动物给药体积 | ul | |
动物数量 | 只 |
| 第二步：请输入动物体内配方组成（配方适用于不溶于水的药物；不同批次药物配方比例不同，请联系GLPBIO为您提供正确的澄清溶液配方） | ||||||||||
| % DMSO % % Tween 80 % saline | ||||||||||
| 计算重置 | ||||||||||
计算结果:
工作液浓度： mg/ml；
DMSO母液配制方法： mg 药物溶于 μL DMSO溶液（母液浓度 mg/mL，
体内配方配制方法：取 μL DMSO母液，加入 μL PEG300，混匀澄清后加入μL Tween 80，混匀澄清后加入 μL saline，混匀澄清。
1. 首先保证母液是澄清的；
2.
一定要按照顺序依次将溶剂加入，进行下一步操作之前必须保证上一步操作得到的是澄清的溶液，可采用涡旋、超声或水浴加热等物理方法助溶。
3. 以上所有助溶剂都可在 GlpBio 网站选购。
Synthesis of biotinylated Episilvestrol: highly selective targeting of the translation factors eIF4AI/II
Org Lett 2013 Mar 15;15(6):1406-9.PMID:23461621DOI:10.1021/ol400401d.
Silvestrol (1) and Episilvestrol (2) are protein synthesis inhibitors, and the former has shown efficacy in multiple mouse models of cancer; however, the selectivity of these potent cytotoxic natural products has not been described. Herein, it is demonstrated that eukaryotic initiation factors eIF4AI/II were the only proteins detected to bind silvestrol (1) and biotinylated Episilvestrol (9) by affinity purification. Our study demonstrates the remarkable selectivity of these promising chemotherapeutics.
Inhibition of nasopharyngeal carcinoma cell proliferation and synergism of cisplatin with silvestrol and Episilvestrol isolated from Aglaia stellatopilosa
Exp Ther Med 2016 Jun;11(6):2117-2126.PMID:27284293DOI:10.3892/etm.2016.3201.
Nasopharyngeal carcinoma (NPC) is a type of tumour that arises from the epithelial cells that line the surface of the nasopharynx. NPC is treated with radiotherapy and cytotoxic chemotherapeutic drugs such as cisplatin and 5-fluorouracil. However, current strategies are often associated with potential toxicities. This has prompted efforts to identify alternative methods of treatment. The present study aimed to investigate silvestrol and episilvestrol-mediated inhibition of cell proliferation in human NPC cells. The growth kinetics of NPC cells treated with silvestrol or Episilvestrol were monitored dynamically using a real-time, impedance-based cell analyzer, and dose-response profiles were generated using a colorimetric cell viability assay. Furthermore, apoptosis was evaluated using flow cytometry and high content analysis. In addition, flow cytometry was performed to determine cell cycle distribution. Finally, the effects of combining silvestrol or Episilvestrol with cisplatin on NPC cells was examined. Apoptosis was not observed in silvestrol and episilvestrol-treated NPC cells, although cell cycle perturbation was evident. Treatment with both compounds induced a significant increase in the percentage of cells in the G2/M phase, as compared with the control. In vitro cultures combining silvestrol or Episilvestrol with cisplatin showed synergistic effects against NPC cells. The results of the present study suggested that silvestrol and Episilvestrol had an anti-tumour activity in NPC cells. Silvestrol and Episilvestrol, particularly in combination with cisplatin, merit further investigation, so as to determine the cellular mechanisms underlying their action(s) as anti-NPC agents.
Silvestrol and Episilvestrol, potential anticancer rocaglate derivatives from Aglaia silvestris
J Org Chem 2004 May 14;69(10):3350-8.PMID:15132542DOI:10.1021/jo040120f.
Two cytotoxic rocaglate derivatives possessing an unusual dioxanyloxy unit, silvestrol (1) and Episilvestrol (2), were isolated from the fruits and twigs of Aglaia silvestris by bioassay-guided fractionation monitored with a human oral epidermoid carcinoma (KB) cell line. Additionally, two new baccharane-type triterpenoids, 17,24-epoxy-25-hydroxybaccharan-3-one (3) and 17,24-epoxy-25-hydroxy-3-oxobaccharan-21-oic acid (4), as well as eleven known compounds, 1beta,6alpha-dihydroxy-4(15)-eudesmene (5), ferulic acid (6), grasshopper ketone (7), apigenin, cabraleone, chrysoeriol, 1beta,4beta-dihydroxy-6alpha,15alpha-epoxyeudesmane, 4-hydroxy-3-methoxyacetophenone, 4-hydroxyphenethyl alcohol, ocotillone, and beta-sitosterol 3-O-beta-D-glucopyranoside, were also isolated and characterized. The structures of compounds 1-4 were elucidated by spectroscopic studies and by chemical transformation. The absolute stereochemistry of silvestrol (1) was established by a X-ray diffraction study of its di-p-bromobenzoate derivative, and the structure of 3 was also confirmed by single-crystal X-ray diffraction. The isolates and chemical transformation products were evaluated for cytotoxicity against several human cancer cell lines, and silvestrol (1) and Episilvestrol (2) exhibited potent in vitro cytotoxic activity. Silvestrol (1) was further evaluated in vivo in the hollow fiber test and in the murine P-388 leukemia model.
Total synthesis of the potent anticancer Aglaia metabolites (-)-silvestrol and (-)-episilvestrol and the active analogue (-)-4'-desmethoxyepisilvestrol
J Am Chem Soc 2009 Feb 4;131(4):1607-16.PMID:19140688DOI:10.1021/ja808402e.
Total synthesis of the anticancer 1,4-dioxane containing natural products silvestrol (1) and Episilvestrol (2) is described by an approach based on the proposed biosynthesis of these novel compounds. The key steps included an oxidative rearrangement of the protected d-glucose derivative 11 to afford the 1,4-dioxane 12, which could be elaborated to the coupling partner 5 and a photochemical [3 + 2]-cycloadditon between the 3-hydroxyflavone 27 and methyl cinnamate followed by base-induced alpha-ketol rearrangement and reduction to give the cyclopentabenzofuran core 33. The core (-)-6 and 1,4-dioxane fragment 5 were united by a highly stereoselective Mitsunobu coupling with the modified azodicarboxylate DMEAD to afford the axial coupled product 36. Deprotection then gave Episilvestrol (2). Silvestrol (1) was synthesized by a coupling between core (-)-6 and the dioxane 44 followed by deprotection. Compound 1 was also synthesized from Episilvestrol (2) by a Mitsunobu inversion. In addition, the analogue 4'-desmethoxyepisilvestrol (46) was synthesized via the same route. It was found that 46 and Episilvestrol 2 displayed an unexpected concentration-dependent chemical shift variation for the nonexchangeable dioxane protons. Synthetic compounds 1, 2, 38, 46, and 54 were tested against cancer cells lines, and it was found that the stereochemistry of the core was critical for activity. Synthetic analogue 4'-desmethoxyepisilvestrol (46) was also active against lung and colon cancer cell lines.
Structurally Modified Cyclopenta[ b]benzofuran Analogues Isolated from Aglaia perviridis
J Nat Prod 2019 Oct 25;82(10):2870-2877.PMID:31621322DOI:10.1021/acs.jnatprod.9b00631.
Four new cyclopenta[b]benzofuran derivatives based on an unprecedented carbon skeleton (1-4), with a dihydrofuran ring fused to dioxanyl and aryl rings, along with a new structural analogue (5) of 5‴-episilvestrol (Episilvestrol, 7), were isolated from an aqueous extract of a large-scale re-collection of the roots of Aglaia perviridis collected in Vietnam. Compound 5 demonstrated mutarotation in solution due to the presence of a hydroxy group at C-2‴, leading to the isolation of a racemic mixture, despite being purified on a chiral-phase HPLC column. Silvestrol (6) and Episilvestrol (7) were isolated from the most potently cytotoxic chloroform subfraction of the roots. All new structures were elucidated using 1D and 2D NMR, HRESIMS, IR, UV, and ECD spectroscopic data. Of the five newly isolated compounds, only compound 5 exhibited cytotoxic activity against a human colon cancer (HT-29) and human prostate cancer cell line (PC-3), with IC50 values of 2.3 μM in both cases. The isolated compounds (1-5) double the number of dioxanyl ring-containing rocaglate analogues reported to date from Aglaia species and present additional information on the structural requirements for cancer cell line cytotoxicity within this compound class.