Altenusin
(Synonyms: 细格菌素,Alutenusin) 目录号 : GC40024A fungal metabolite with diverse biological activities
Cas No.:31186-12-6
Sample solution is provided at 25 µL, 10mM.
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Quality Control & SDS
- View current batch:
- Purity: >98.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Altenusin is a polyphenol fungal metabolite originally isolated from the fungus Alternaria that has diverse biological activities.[1][2] It inhibits Src kinase with an IC50 value of 20 nM.[3] Altenusin inhibits fibrillization of recombinant tau fragments in vitro and phosphorylation of tau in SH-SY5Y cells expressing human P301L mutant tau when used at a concentration of 10 μM. [1] It is an agonist of the farnesoid X receptor (FXR; EC50 = 3.2 μM) that reduces blood glucose, serum insulin, and serum cholesterol levels, as well as hepatic lipogenic gene expression and steatosis, in a high fat diet-induced mouse model of obesity when administered at 30 mg/kg per day. Altenusin also has antioxidant and antifungal properties.
Reference:
[1]. Chua, S.W., Cornejo, A., van Eersel, J., et al. The polyphenol altenusin inhibits in vitro fibrillization of tau and reduces induced tau pathology in primary neurons. ACS Chem. Neurosci. 8(4), 743-751 (2017).
[2]. Zheng, Z., Zhao, Z., Li, S., et al. Altenusin, a nonsteroidal microbial metabolite, attenuates nonalcoholic fatty liver disease by activating the farnesoid X receptor. Mol. Pharmacol. 92(4), 425-436 (2017).
[3]. Oyama, M., Xu, Z., Lee, K.-H., et al. Fungal metabolites as potent protein kinase inhibitors: Identification of a novel metabolite and novel activities of known metabolites. Lett. Drug. Des. Discov. 100(1), 24-29 (2004).
| Cas No. | 31186-12-6 | SDF | |
| 别名 | 细格菌素,Alutenusin | ||
| 化学名 | 3,4',5'-trihydroxy-5-methoxy-2'-methyl-[1,1'-biphenyl]-2-carboxylic acid | ||
| Canonical SMILES | COC1=CC(C2=C(C)C=C(O)C(O)=C2)=C(C(O)=O)C(O)=C1 | ||
| 分子式 | C15H14O6 | 分子量 | 290.3 |
| 溶解度 | DMSO: soluble,Ethanol: soluble,Methanol: soluble | 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 | 3.4447 mL | 17.2236 mL | 34.4471 mL |
| 5 mM | 0.6889 mL | 3.4447 mL | 6.8894 mL |
| 10 mM | 0.3445 mL | 1.7224 mL | 3.4447 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。
Altenusin, a Nonsteroidal Microbial Metabolite, Attenuates Nonalcoholic Fatty Liver Disease by Activating the Farnesoid X Receptor
Mol Pharmacol 2017 Oct;92(4):425-436.PMID:28739572DOI:10.1124/mol.117.108829.
Nonalcoholic fatty liver disease (NAFLD) is a prevalent chronic liver disease. The incidence of NAFLD has increased steadily due to its close association with the global epidemic of obesity and type 2 diabetes. However, there is no effective pharmacological therapy approved for NAFLD. Farnesoid X receptor (FXR), a member of the nuclear receptor subfamily, plays important roles in maintaining the homeostasis of bile acids, glucose, and lipids. FXR agonists have shown promise for the treatment of NAFLD. In this study, we report Altenusin (2076A), a natural nonsteroidal fungal metabolite, as a novel selective agonist of FXR with an EC50 value of 3.2 ± 0.2 μM. Administration of 2076A protected mice from high-fat diet (HFD)-induced obesity by reducing the body weight and fat mass by 22.9% and 50.0%, respectively. Administration of 2076A also decreased the blood glucose level from 178.3 ± 12.4 mg/dl to 116.2 ± 4.1 mg/dl and the serum insulin level from 1.4 ± 0.6 ng/dl to 0.4 ± 0.1 ng/dl. Moreover, 2076A treatment nearly reversed HFD-induced hepatic lipid droplet accumulation and macrovesicular steatosis. These metabolic effects were abolished in FXR knockout mice. Mechanistically, the metabolic benefits of 2076A might have been accounted for by the increased insulin sensitivity and suppression of genes that are involved in hepatic gluconeogenesis and lipogenesis. In summary, we have uncovered a new class of nonsteroidal FXR agonist that shows promise in treating NAFLD and the associated metabolic syndrome.
Two New Altenusin/Thiazole Hybrids and a New Benzothiazole Derivative from the Marine Sponge-Derived Fungus Alternaria sp. SCSIOS02F49
Molecules 2018 Nov 1;23(11):2844.PMID:30388842DOI:10.3390/molecules23112844.
Two novel altenusin-thiazole hybrids named altenusinoides A and B (1 and 2), a new benzothiazole derivative (3), and three known Altenusin derivatives (4?6) have been obtained from the solid culture of the marine sponge-derived fungal strain, Alternaria sp. SCSIOS02F49. The structures of these new compounds were characterized by NMR, HRESIMS, and X-ray single crystal analysis. Compounds 1 and 2 possess an unusual altenusin-thiazole-fused skeleton core (6/6/5), and compound 3 represents the first benzothiazole derivative from fungi. Compounds 4 and 5 showed significant DPPH free-radical-scavenging activities with the prominent IC50 values of 10.7 ± 0.09 μM and 100.6 ± 0.025 μM, respectively. Additionally, compound 5 exhibited COX-2 inhibitory activity with an IC50 value of 9.5 ± 0.08 μM.
The Polyphenol Altenusin Inhibits in Vitro Fibrillization of Tau and Reduces Induced Tau Pathology in Primary Neurons
ACS Chem Neurosci 2017 Apr 19;8(4):743-751.PMID:28067492DOI:10.1021/acschemneuro.6b00433.
In Alzheimer's disease, the microtubule-associated protein tau forms intracellular neurofibrillary tangles (NFTs). A critical step in the formation of NFTs is the conversion of soluble tau into insoluble filaments. Accordingly, a current therapeutic strategy in clinical trials is aimed at preventing tau aggregation. Here, we assessed Altenusin, a bioactive polyphenolic compound, for its potential to inhibit tau aggregation. Altenusin inhibits aggregation of tau protein into paired helical filaments in vitro. This was associated with stabilization of tau dimers and other oligomers into globular structures as revealed by atomic force microscopy. Moreover, Altenusin reduced tau phosphorylation in cells expressing pathogenic tau, and prevented neuritic tau pathology induced by incubation of primary neurons with tau fibrils. However, treatment of tau transgenic mice did not improve neuropathology and functional deficits. Taken together, Altenusin prevents tau fibrillization in vitro and induced tau pathology in neurons.
Antifungal activity of Altenusin isolated from the endophytic fungus Alternaria sp. against the pathogenic fungus Paracoccidioides brasiliensis
Rev Iberoam Micol 2012 Oct-Dec;29(4):205-9.PMID:22366718DOI:10.1016/j.riam.2012.02.002.
Background: Altenusin is a biphenyl derivative isolated from different species of fungi, which presents several biological activities. Aims: We report the antifungal activity of the Altenusin isolated from the endophytic fungus Alternaria sp., against clinical isolates of Paracoccidioides brasiliensis, and its action on cell walls of P. brasiliensis and the nonpathogenic yeast Schizosaccharomyces pombe. Methods: In vitro antifungal activity of Altenusin was evaluated using the broth microdilution method against 11 strains of P. brasiliensis and one strain of S. pombe. The effects of the Altenusin on the cell wall were estimated using the sorbitol protection assay. Results: The Altenusin presented strong activity against P. brasiliensis with MIC values ranging between 1.9 and 31.2 μg/ml, and 62.5 μg/ml for S. pombe. Our results demonstrated that the MIC values for Altenusin were increased for P. brasiliensis Pb18 and for S. pombe when the medium was supplemented with sorbitol. Additionally, S. pombe cells treated with Altenusin were more rounded in shape than untreated cells. Conclusions: Altenusin showed activity against clinical strains of P. brasiliensis at the concentration tested, and this compound probably affects fungal cell walls. These findings suggest that Altenusin could act through the inhibition of cell wall synthesis or assembly in P. brasiliensis and S. pombe, and could be considered as a lead compound for the design of new antifungals.
Altenusin, a biphenyl isolated from the endophytic fungus Alternaria sp., inhibits trypanothione reductase from Trypanosoma cruzi
FEMS Microbiol Lett 2008 Aug;285(2):177-82.PMID:18557945DOI:10.1111/j.1574-6968.2008.01221.x.
Parasitic protozoan species belonging to the genera Trypanosoma and Leishmania are the etiological agents of several diseases in tropical areas of the world, for which there is an urgent need for effective and affordable treatment. In this regard, we are screening the Brazilian biodiversity, especially its flora and mycota, for natural products that could serve as leads for drug development against these diseases. Trypanothione reductase (TR) is an enzyme involved in the protection of Trypanosoma and Leishmania species against oxidative stress, and is considered to be a validated drug target. The endophytic fungus Alternaria sp. (UFMGCB55) was isolated from the plant Trixis vauthieri DC (Asteraceae), known to contain trypanocidal compounds. The organic extract of the culture of Alternaria sp. was able to inhibit TR by 99%, when tested at 20 microg mL(-1). Fractionation of the extract identified Altenusin, a biphenyl derivative with an IC50 value of 4.3+/-0.3 microM in the TR assay. This compound is the first in its class to have shown TR inhibitory activity, opening new perspectives for the design of more effective derivatives that could serve as drug leads for new chemotherapeutic agents to treat trypanosomiasis and leishmaniasis.