Stephacidin B
(Synonyms: (–)-Stephacidin B) 目录号 : GC48354
A fungal metabolite
Cas No.:360765-75-9
Sample solution is provided at 25 µL, 10mM.
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Quality Control & SDS
- View current batch:
- Purity: >95.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Stephacidin B is a fungal metabolite that has been found in A. ochraceus.1 Dimeric stephacidin B is rapidly converted to a monomer, avrainvillamide , in vitro.2 Stephacidin B is cytotoxic to a variety of cancer cells, including testosterone-independent PC3 and -sensitive LNCaP prostate cancer cells (IC50s = 0.37 and 0.06 µM, respectively) and estradiol-independent SK-BR-3 and -sensitive MCF-7 breast cancer cells (IC50s = 0.32 and 0.27 µM, respectively).1 It induces apoptosis in HepG2 and Huh7 hepatocellular carcinoma cells when used at a concentration of 4 µM.3
1.Qian-Cutrone, J., Huang, S., Shu, Y.-Z., et al.Stephacidin A and B: Two structurally novel, selective inhibitors of the testosterone-dependent prostate LNCaP cellsJ. Am. Chem. Soc.124(49)14556-14557(2002) 2.Wulff, J.E., Herzon, S.B., Siegrist, R., et al.Evidence for the rapid conversion of stephacidin B into the electrophilic monomer avrainvillamide in cell cultureJ. Am. Chem. Soc.129(16)4898-4899(2007) 3.Hu, L., Zhang, T., Liu, D., et al.Notoamide-type alkaloid induced apoptosis and autophagy via a P38/JNK signaling pathway in hepatocellular carcinoma cellsRSC Adv.9(34)19855-19868(2019)
| Cas No. | 360765-75-9 | SDF | |
| 别名 | (–)-Stephacidin B | ||
| Canonical SMILES | CC1(C(C2(C3=CC=C(O4)C(C=CC4(C)C)=C35)[C@@](C(C6=CC=C(O7)C(C=CC7(C)C)=C6N8O)=C8C9(C)C)([H])[C@]([C@@]9([H])C[C@@]%10%11C%12=O)(C(N%10CCC%11)=O)N%12[C@@]2([H])[C@]%13(NC%14=O)[C@@]1([H])CC%14%15N(CCC%15)C%13=O)=[N]5=O)C | ||
| 分子式 | C52H54N6O8 | 分子量 | 891 |
| 溶解度 | 储存条件 | -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 | 1.1223 mL | 5.6117 mL | 11.2233 mL |
| 5 mM | 0.2245 mL | 1.1223 mL | 2.2447 mL |
| 10 mM | 0.1122 mL | 0.5612 mL | 1.1223 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。
Enantioselective synthesis of Stephacidin B
J Am Chem Soc 2005 Apr 20;127(15):5342-4.PMID:15826171DOI:10.1021/ja0510616.
We describe an enantioselective synthetic route to the antiproliferative alkaloid Stephacidin B (1) proceeding in 18 steps and 4.0% yield from 4,4-(ethylenedioxy)-2,2-dimethylcyclohexanone (3). Key features of the synthetic sequence include the use of the Corey-Bakshi-Shibata (CBS) reduction to introduce asymmetry early in the synthetic route, use of the novel electrophile N-(tert-butoxycarbonyl)-5-(isopropylsulfonyloxymethyl)-2,3-dihydropyrrole in a stereoselective enolate alkylation, a diastereoselective Strecker-type addition of hydrogen cyanide to an N-Boc enamine substrate in the solvent hexafluoroisopropanol, platinum-catalyzed nitrile hydrolysis under neutral conditions, cyclization of an acylamino radical intermediate to form the diketopiperazine core of Stephacidin B, and implementation of a convergent procedure for introduction of the key 3-alkylidene-3H-indole 1-oxide functional group in the final stage of the route to prepare the structure 2, previously proposed to be the fungal metabolite avrainvillamide (17 steps, 4.2% yield). We observed that synthetic (-)-2 dimerized in the presence of triethylamine to form (+)-stephacidin B (>95%). We also obtained evidence that 2 can form 1 under mild conditions, and that 2 reacts with nucleophiles, such as methanol, by conjugate addition.
Stephacidin A and B: two structurally novel, selective inhibitors of the testosterone-dependent prostate LNCaP cells
J Am Chem Soc 2002 Dec 11;124(49):14556-7.PMID:12465964DOI:10.1021/ja028538n.
Two novel antitumor alkaloids, Stephacidin A and B, were isolated from the solid fermentation of Aspergillus ochraceus WC76466. Both alkaloids exhibit in vitro cytotoxicity against a number of human tumor cell lines; however, Stephacidin B demonstrated more potent and selective antitumor activities, especially against prostate testeosterone-dependent LNCaP cells with IC50 value of 60 nM. The structures of stephacidin A and B were established on the basis of the NMR data and X-ray crystallography. With 15 rings and 9 chiral centers, Stephacidin B represents one of the most structurally complex and novel alkaloids occurring in nature.
Recent synthetic approaches towards the antiproliferative natural products avrainvillamide and Stephacidin B
Chem Soc Rev 2010 Feb;39(2):591-9.PMID:20111783DOI:10.1039/b900407f.
Due to their strong antiproliferative activity and their unprecedented structural complexity within the class of indole alkaloids, avrainvillamide and Stephacidin B have recently attracted considerable interest from the synthetic community. To date, three distinct approaches towards these molecules have been disclosed and the present tutorial review aims at comparing all three syntheses with a focus on the various strategies and methods employed. Besides, recent progress towards the synthesis of structural analogs and the identification of the biological target of avrainvillamide will be presented.
Toxic indole alkaloids avrainvillamide and Stephacidin B produced by a biocide tolerant indoor mold Aspergillus westerdijkiae
Toxicon 2015 Jun 1;99:58-67.PMID:25804991DOI:10.1016/j.toxicon.2015.03.011.
Toxic Aspergillus westerdijkiae were present in house dust and indoor air fall-out from a residence and a kindergarten where the occupants suffered from building related ill health. The A. westerdijkiae isolates produced indole alkaloids avrainvillamide (445 Da) and its dimer Stephacidin B (890 Da). It grew and sporulated in presence of high concentrations of boron or polyguanidine (PHMB, PHMG) based antimicrobial biocides used to remediate mold infested buildings. The boar sperm cells were used as sensor cells to purify toxins from HPLC fractions of the fungal biomass. Submicromolar concentrations (EC50 0.3-0.4 μM) blocked boar spermatozoan motility and killed porcine kidney tubular epithelial cells (PK-15). Plate grown hyphal mass of the A. westerdijkiae isolates contained 300-750 ng of avrainvillamide and 30-300 ng of Stephacidin B per mg (wet weight). The toxins induced rapid (30 min) loss of boar sperm motility, followed (24 h) by loss of mitochondrial membrane potential (ΔΨm). Apoptotic cell death was observed in PK-15 cell monolayers, prior to cessation of glucose uptake or loss of ΔΨm. Avrainvillamide and Stephacidin B were 100-fold more potent towards the porcine cells than the mycotoxins stephacidin A, ochratoxin A, sterigmatocystin and citrinin. The high toxicity of Stephacidin B indicates a role of nitrone group in the mechanism of toxicity. Avrainvillamide and Stephacidin B represent a new class of toxins with possible a threat to human health in buildings. Furthermore, the use of biocides highly enhanced the growth of toxigenic A. westerdijkiae.
Evidence for the rapid conversion of Stephacidin B into the electrophilic monomer avrainvillamide in cell culture
J Am Chem Soc 2007 Apr 25;129(16):4898-9.PMID:17397160DOI:10.1021/ja0690971.
We report that the dimeric alkaloid Stephacidin B (1) and the monomeric alkaloid avrainvillamide (2) function equivalently within experimental error to inhibit the growth of four different cultured human cancer cell lines. We also show that the proportion of the monomer greatly outweighs that of the dimer in the medium of incubation, and that the half-life for the transformation of 1 to 2 is short relative to the half-life of cell division. Finally, using a monomer-based affinity reagent, we provide evidence that the monomer (2) interacts with intracellular thiol-containing proteins, likely by covalent modification.