Diphyllin
(Synonyms: 二叶草素) 目录号 : GC39734
A lignan with diverse biological activities
Cas No.:22055-22-7
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
Diphyllin is a lignan that has been found in C. collinus and has diverse biological activities.1,2,3 It reduces viral titers in Vero cells infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2; EC50 = 1.92 ?M).1 It inhibits bovine chromaffin granule V-ATPase (IC50 = 17 nM) and lysosomal acidification in primary human osteoclasts.2 Diphyllin (1, 5, and 10 ?M) induces apoptosis in and inhibits the growth of SGC-7901 gastric adenocarcinoma cells.3 In vivo, diphyllin (20 mg/kg) reduces intratumoral expression of V-ATPase and tumor volume in an SGC-7901 mouse xenograft model.
1.Stefanik, M., Strakova, P., Haviernik, J., et al.Antiviral activity of vacuolar ATPase blocker diphyllin against SARS-CoV-2Microorganisms9(3)471(2021) 2.Sorensen, M.G., Henriksen, K., Neutzsky-Wulff, A.V., et al.Diphyllin, a novel and naturally potent V-ATPase inhibitor, abrogates acidification of the osteoclastic resorption lacunae and bone resorptionJ. Bone Miner. Res.22(10)1640-1648(2007) 3.Shen, W., Zou, X., Chen, M., et al.Effects of diphyllin as a novel V-ATPase inhibitor on gastric adenocarcinomaEur. J. Pharmacol.667(1-3)330-338(2011)
| Cas No. | 22055-22-7 | SDF | |
| 别名 | 二叶草素 | ||
| Canonical SMILES | O=C1OCC2=C(O)C3=CC(OC)=C(OC)C=C3C(C4=CC=C(OCO5)C5=C4)=C12 | ||
| 分子式 | C21H16O7 | 分子量 | 380.35 |
| 溶解度 | DMSO : 14.29 mg/mL (37.57 mM; Need ultrasonic) | 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 | 2.6292 mL | 13.1458 mL | 26.2916 mL |
| 5 mM | 0.5258 mL | 2.6292 mL | 5.2583 mL |
| 10 mM | 0.2629 mL | 1.3146 mL | 2.6292 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。
Diphyllin Shows a Broad-Spectrum Antiviral Activity against Multiple Medically Important Enveloped RNA and DNA Viruses
Viruses 2022 Feb 9;14(2):354.PMID:35215947DOI:10.3390/v14020354.
Diphyllin is a natural arylnaphtalide lignan extracted from tropical plants of particular importance in traditional Chinese medicine. This compound has been described as a potent inhibitor of vacuolar (H+)ATPases and hence of the endosomal acidification process that is required by numerous enveloped viruses to trigger their respective viral infection cascades after entering host cells by receptor-mediated endocytosis. Accordingly, we report here a revised, updated, and improved synthesis of Diphyllin, and demonstrate its antiviral activities against a panel of enveloped viruses from Flaviviridae, Phenuiviridae, Rhabdoviridae, and Herpesviridae families. Diphyllin is not cytotoxic for Vero and BHK-21 cells up to 100 µM and exerts a sub-micromolar or low-micromolar antiviral activity against tick-borne encephalitis virus, West Nile virus, Zika virus, Rift Valley fever virus, rabies virus, and herpes-simplex virus type 1. Our study shows that Diphyllin is a broad-spectrum host cell-targeting antiviral agent that blocks the replication of multiple phylogenetically unrelated enveloped RNA and DNA viruses. In support of this, we also demonstrate that Diphyllin is more than just a vacuolar (H+)ATPase inhibitor but may employ other antiviral mechanisms of action to inhibit the replication cycles of those viruses that do not enter host cells by endocytosis followed by low pH-dependent membrane fusion.
2, 4, 5-Trideoxyhexopyranosides derivatives of Diphyllin: Synthesis and anticancer activity
Chem Biol Drug Des 2022 Aug;100(2):256-266.PMID:35614538DOI:10.1111/cbdd.14095.
Diphyllin and its natural derivatives were identified as potent vacuolar H+ -ATPase (V-ATPase) inhibitors. In this study, twelve 2, 4, 5-trideoxyhexopyranosides derivatives of Diphyllin were synthesized. Most of these compounds showed potent abilities to inhibit the growth of HT-29, MCF-7, HepG2 cancer cells with IC50 values at submicromolar concentration. The compounds 5c3 and 5c4 showed the best inhibitory activity on breast cancer cell lines MCF-7 with IC50 values of 0.09 and 0.10 μM. Compounds 5c3 and 5c4 showed similar V-ATPase inhibitory potency to Diphyllin. Molecular docking showed that a hydrogen bond was found between the hydroxyl of 5c3 and SerA534 in the pocket of the V-ATPase receptor.
Antiviral Activity of Vacuolar ATPase Blocker Diphyllin against SARS-CoV-2
Microorganisms 2021 Feb 25;9(3):471.PMID:33668694DOI:10.3390/microorganisms9030471.
Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) is a causative agent of the pandemic coronavirus disease 2019 (COVID-19), which has resulted in over two million deaths worldwide to date. Diphyllin and diphyllinosides are known as natural blockers of cellular vacuolar ATPases, and so can act as inhibitors of the pH-dependent fusion of viral envelopes with host cell endosomal membranes. Such pH-dependent fusion is a critical early step during the SARS-CoV-2 replication cycle. Accordingly, the anti-SARS-CoV-2 profiles and cytotoxicities of Diphyllin, diphyllinoside cleistanthin B, and two structurally related compounds, helioxanthin 8-1 and helioxanthin 5-4-2, are evaluated here using in vitro cell-based assay systems. Neither helioxanthin exhibits any obvious anti-SARS-CoV-2 effects in vitro. By contrast Diphyllin and cleistanthin B do exhibit anti-SARS-CoV-2 effects in Vero cells, with respective 50% effective concentrations (EC50) values of 1.92 and 6.51 µM. Diphyllin displays anti-SARS-CoV-2 effect also in colorectal adenocarcinoma (CaCo-2) cells. Moreover, when Diphyllin is added at various times post infection, a significant decrease in viral titer is observed in SARS-CoV-2-infected Vero cells, even at high viral multiplicities of infection. Importantly, neither Diphyllin nor cleistanthin B are found cytotoxic to Vero cells in concentrations up to 100 µM. However, the cytotoxic effect of Diphyllin is more pronounced in Vero E6 and CaCo-2 cells. Overall, our data demonstrate that Diphyllin and Diphyllin analogues might be perfected as anti-SARS-CoV-2 agents in future preclinical studies, most especially if nanomedicine approaches may be invoked to optimize functional drug delivery to virus infected cells.
Diphyllin Improves High-Fat Diet-Induced Obesity in Mice Through Brown and Beige Adipocytes
Front Endocrinol (Lausanne) 2020 Dec 10;11:592818.PMID:33424769DOI:10.3389/fendo.2020.592818.
Brown adipose tissue (BAT) and beige adipose tissue dissipate metabolic energy and mediate nonshivering thermogenesis, thereby boosting energy expenditure. Increasing the browning of BAT and beige adipose tissue is expected to be a promising strategy for combatting obesity. Through phenotype screening of C3H10-T1/2 mesenchymal stem cells, Diphyllin was identified as a promising molecule in promoting brown adipocyte differentiation. In vitro studies revealed that Diphyllin promoted C3H10-T1/2 cell and primary brown/beige preadipocyte differentiation and thermogenesis, which resulted increased energy consumption. We synthesized the compound and evaluated its effect on metabolism in vivo. Chronic experiments revealed that mice fed a high-fat diet (HFD) with 100 mg/kg Diphyllin had ameliorated oral glucose tolerance and insulin sensitivity and decreased body weight and fat content ratio. Adaptive thermogenesis in HFD-fed mice under cold stimulation and whole-body energy expenditure were augmented after chronic Diphyllin treatment. Diphyllin may be involved in regulating the development of brown and beige adipocytes by inhibiting V-ATPase and reducing intracellular autophagy. This study provides new clues for the discovery of anti-obesity molecules from natural products.
Synthesis, Cytotoxicity, Anti-Migration and Anti-Invasion Activity of Diphyllin Heterocyclic Derivatives
Med Chem 2022;18(1):122-129.PMID:33349219DOI:10.2174/1573406417666201221160220.
Background: Diphyllin, an arylnaphthalene lignan lactone, isolated from many traditional medicinal plants, has been reported to possess anticancer and antiviral activities. Natural Diphyllin and its glycosides were identified as potent vacuolar H+-ATPase (V-ATPase) inhibitors. Objective: The aim of this study was to design and synthesize a series of heterocyclic derivatives of Diphyllin as novel anticancer agents. Methods: The targeted heterocyclic derivatives of Diphyllin were synthesized from Diphyllin employing etherification reaction and N-substitution reaction. Cytotoxicity of these compounds on four cancer cells was assessed by MTT assay. The inhibitory activity of V-ATPase of compound 3n was measured on MGC-803 cells. Anti-migration and anti-invasion abilities were assessed by transwell invasion assay and scratch wound assay. Results: Most of these derivatives displayed potent cytotoxicity on four cancer cells at submicromolar concentrations. The most potent derivative 3n has been shown to inhibit V-ATPase activity, migration and invasion abilities on MGC-803 cells at 0.75 μM. Conclusion: The collective results clearly indicate that heterocyclic derivatives of Diphyllin inhibit the viability, V-ATPase activity, migration and invasion of the MGC803 cells. The current findings provide valuable insights for the future development of novel Diphyllin derivatives as anticancer agents.