Thiocoraline
(Synonyms: PM 93135) 目录号 : GC48165
A depsipeptide and DNA bis-intercalator with antibacterial and anticancer activities
Cas No.:173046-02-1
Sample solution is provided at 25 µL, 10mM.
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Quality Control & SDS
- View current batch:
- Purity: >70.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Thiocoraline is a depsipeptide and DNA bis-intercalator originally isolated from Micromonospora with antibacterial and anticancer activities.1,2 It is active against the Gram-positive bacteria S. aureus, B. subtilis, and M. luteus (MICs = 0.05, 0.05, and 0.03 µg/ml, respectively) but not Gram-negative E. coli, K. pneumoniae, or P. aeruginosa (MICs = >100 µg/ml for all).1 Thiocoraline inhibits RNA and DNA polymerase and thymidylate synthase (IC50s = 6, 6, and 15 µg/ml, respectively), as well as RNA and DNA synthesis in vitro (IC50s = 0.008 and 0.4 µg/ml, respectively). It is cytotoxic to P388, A549, HT-29, and MEL-28 cancer cells (IC50s = 0.002, 0.002, 0.01, and 0.002 µg/ml, respectively).
1.Romero, F., Espilego, F., PÉrez Baz, J., et al.Thiocoraline, a new depsipeptide with antitumor activity produced by a marine Micromonospora. I. Taxonomy, fermentation, isolation, and biological activitiesJ. Antibiot. (Tokyo)50(9)734-737(1997) 2.Negri, A., Marco, E., GarcÍa-HernÁndez, V., et al.Antitumor activity, X-ray crystal structure, and DNA binding properties of thiocoraline A, a natural bisintercalating thiodepsipeptideJ. Med. Chem.50(14)3322-3333(2007)
| Cas No. | 173046-02-1 | SDF | |
| 别名 | PM 93135 | ||
| Canonical SMILES | O=C([C@H](CSC)N(C([C@H]1N(C)C(CNC([C@H](NC(C2=NC(C=CC=C3)=C3C=C2O)=O)CSC([C@H](CSC)N(C)C([C@H](CSSC1)N4C)=O)=O)=O)=O)=O)C)SC[C@@H](NC(C5=NC(C=CC=C6)=C6C=C5O)=O)C(NCC4=O)=O | ||
| 分子式 | C48H56N10O12S6 | 分子量 | 1157.4 |
| 溶解度 | Dichloromethane: soluble,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 | 0.864 mL | 4.32 mL | 8.6401 mL |
| 5 mM | 0.1728 mL | 0.864 mL | 1.728 mL |
| 10 mM | 0.0864 mL | 0.432 mL | 0.864 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。
Thiocoraline mediates drug resistance in MCF-7 cells via PI3K/Akt/BCRP signaling pathway
Cytotechnology 2019 Feb;71(1):401-409.PMID:30689149DOI:10.1007/s10616-019-00301-w.
Thiocoraline, a depsipeptide bisintercalator with potent antitumor activity, was first isolated from marine actinomycete Micromonospora marina. It possesses an intense toxicity to MCF-7 cells at nanomolar concentrations in a dose-dependent manner evaluated by MTT assay and crystal violet staining. We established a human breast thiocoraline-resistant cancer subline of MCF-7/Thiocoraline (MCF-7/T) to investigate the expression variation of breast cancer resistance proteins (BCRP) and its subsequent influence on drug resistance. Colony-forming assay showed that the MCF-7 cells proliferated faster than the MCF-7/T cells in vitro. Western blot analysis demonstrated that Thiocoraline increased the phosphorylation of Akt. Additionally, the sensitivity of tumor cells to Thiocoraline was reduced with a concurrent rise in phosphorylation level of Akt and of BCRP expression.These studies indicated that Thiocoraline probably mediated the drug resistance via PI3K/Akt/BCRP signaling pathway. MK-2206 dihydrochloride, a selective phosphorylation inhibitor of Akt, significantly decreased MCF-7 cell viability under exposure to Thiocoraline compared to the control. However, it was not obviously able to decrease MCF-7/T cell viability when cells were exposed to Thiocoraline.
Thiocoraline activates the Notch pathway in carcinoids and reduces tumor progression in vivo
Cancer Gene Ther 2014 Dec;21(12):518-25.PMID:25412645DOI:10.1038/cgt.2014.57.
Carcinoids are slow-growing neuroendocrine tumors (NETs) that are characterized by hormone overproduction; surgery is currently the only option for treatment. Activation of the Notch pathway has previously been shown to have a role in tumor suppression in NETs. The marine-derived thiodepsipeptide Thiocoraline was investigated in vitro in two carcinoid cell lines (BON and H727). Carcinoid cells treated with nanomolar concentrations of Thiocoraline resulted in a decrease in cell proliferation and an alteration of malignant phenotype evidenced by decrease of NET markers, achaete-scute complex like-1, chromogranin A and neurospecific enolase. Western blotting analysis demonstrated the activation of Notch1 on the protein level in BON cells. Additionally, Thiocoraline activated downstream Notch targets HES1, HES5 and HEY2. Thiocoraline effectively suppressed carcinoid cell growth by promoting cell cycle arrest in BON and H727 cells. An in vivo study demonstrated that Thiocoraline, formulated with polymeric micelles, slowed carcinoid tumor progression. Thus the therapeutic potential of Thiocoraline, which induced activation of the Notch pathway, in carcinoid tumors was demonstrated.
Thiocoraline alters neuroendocrine phenotype and activates the Notch pathway in MTC-TT cell line
Cancer Med 2013 Oct;2(5):734-43.PMID:24403239DOI:10.1002/cam4.118.
Medullary thyroid cancer (MTC) is an aggressive neuroendocrine tumor (NET). Previous research has shown that activation of Notch signaling has a tumor suppressor role in NETs. The potential therapeutic effect of Thiocoraline on the activation of the Notch pathway in an MTC cell line (TT) was investigated. Thiocoraline was isolated from a marine bacterium Verrucosispora sp. MTT assay (3-[4, 5-dimethylthiazole-2-yl]-2, 5-diphenyltetrazolium bromide) was used to determine the IC50 value and to measure cell proliferation. Western blot revealed the expression of Notch isoforms, NET, and cell cycle markers. Cell cycle progression was validated by flow cytometry. The mRNA expression of Notch isoforms and downstream targets were measured using real-time PCR. The IC50 value for Thiocoraline treatment in TT cells was determined to be 7.6 nmol/L. Thiocoraline treatment decreased cell proliferation in a dose- and time-dependent manner. The mechanism of growth inhibition was found to be cell cycle arrest in G1 phase. Thiocoraline activated the Notch pathway as demonstrated by the dose-dependent increase in mRNA and protein expression of Notch isoforms. Furthermore, treatment with Thiocoraline resulted in changes in the expression of downstream targets of the Notch pathway (HES1, HES2, HES6, HEY1, and HEY2) and reduced expression of NET markers, CgA, and ASCL1. Thiocoraline is a potent Notch pathway activator and an inhibitor of MTC-TT cell proliferation at low nanomolar concentrations. These results provide exciting evidence for the use of Thiocoraline as a potential treatment for intractable MTC.
Activation and Loading of the Starter Unit during Thiocoraline Biosynthesis
Biochemistry 2017 Aug 29;56(34):4457-4467.PMID:28762729DOI:10.1021/acs.biochem.7b00661.
The initiation of the nonribosomal peptide synthetase (NRPS) assembly of the bisintercalator natural product Thiocoraline involves key enzymatic steps for AMP activation and carrier protein loading of the starter unit 3-hydroxyquinaldic acid (3HQA). Gene cluster data combined with protein sequence homology analysis originally led us to propose that TioJ could be responsible for the AMP activation step, whereas TioO could act as the thiolation (T) domain, facilitating the transfer of 3HQA to the next NRPS module, TioR. Herein, we confirmed the involvement of TioJ in Thiocoraline biosynthesis by tioJ knockout and in vitro activation of 3HQA studies. However, we demonstrated that TioJ-activated 3HQA is not loaded onto the T domain TioO, as originally believed, but instead onto a fatty acid synthase (FAS) acyl carrier protein (ACP) domain FabC, which is located outside of the Thiocoraline gene cluster. We showed a strong interaction between TioJ and FabC. By generating TioJ point mutants mimicking the active site of highly homologous enzymes activating different molecules, we showed that the identity of the substrate activated by adenylation domains such as TioJ is not determined by only the active site residues that directly interact with the substrate. The insights gained from these enzymatic transformations are valuable in the efforts toward deciphering the complete biosynthetic pathway of Thiocoraline and bisintercalators in general.
Mode of action of Thiocoraline, a natural marine compound with anti-tumour activity
Br J Cancer 1999 Jun;80(7):971-80.PMID:10362104DOI:10.1038/sj.bjc.6690451.
Thiocoraline, a new anticancer agent derived from the marine actinomycete Micromonospora marina, was found to induce profound perturbations of the cell cycle. On both LoVo and SW620 human colon cancer cell lines, Thiocoraline caused an arrest in G1 phase of the cell cycle and a decrease in the rate of S phase progression towards G2/M phases, as assessed by using bromodeoxyuridine/DNA biparametric flow cytometric analysis. Thiocoraline does not inhibit DNA-topoisomerase II enzymes in vitro, nor does it induce DNA breakage in cells exposed to effective drug concentrations. The cell cycle effects observed after exposure to Thiocoraline appear related to the inhibition of DNA replication. By using a primer extension assay it was found that Thiocoraline inhibited DNA elongation by DNA polymerase alpha at concentrations that inhibited cell cycle progression and clonogenicity. These studies indicate that the new anticancer drug Thiocoraline probably acts by inhibiting DNA polymerase alpha activity.