Thiocoraline
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| Category | Antibiotics |
| Catalog number | BBF-03127 |
| CAS | 173046-02-1 |
| Molecular Weight | 1157.41 |
| Molecular Formula | C48H56N10O12S6 |
| Purity | >98% |
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Description
Thiocoraline is a peptide antibiotic produced by Micromonospora sp. L-13-ACM2-092. It has strong anti-Gram-positive bacteria and weak anti-Gram-negative bacteria activity. The effect of inhibiting RNA synthesis is stronger than that of inhibiting DNA synthesis. Cytotoxic activity.
Specification
| Synonyms | Thicoraline; Thi Coraline |
| Storage | Store at -20°C |
| IUPAC Name | 3-hydroxy-N-[20-[(3-hydroxyquinoline-2-carbonyl)amino]-2,12,15,25-tetramethyl-11,24-bis(methylsulfanylmethyl)-3,6,10,13,16,19,23,26-octaoxo-9,22,28,29-tetrathia-2,5,12,15,18,25-hexazabicyclo[12.12.4]triacontan-7-yl]quinoline-2-carboxamide |
| Canonical SMILES | CN1C2CSSCC(C(=O)N(C(C(=O)SCC(C(=O)NCC1=O)NC(=O)C3=NC4=CC=CC=C4C=C3O)CSC)C)N(C(=O)CNC(=O)C(CSC(=O)C(N(C2=O)C)CSC)NC(=O)C5=NC6=CC=CC=C6C=C5O)C |
| InChI | InChI=1S/C48H56N10O12S6/c1-55-31-23-75-76-24-32(46(68)58(4)34(22-72-6)48(70)74-19-29(41(63)49-17-37(55)61)53-43(65)39-35(59)15-25-11-7-9-13-27(25)51-39)56(2)38(62)18-50-42(64)30(20-73-47(69)33(21-71-5)57(3)45(31)67)54-44(66)40-36(60)16-26-12-8-10-14-28(26)52-40/h7-16,29-34,59-60H,17-24H2,1-6H3,(H,49,63)(H,50,64)(H,53,65)(H,54,66) |
| InChI Key | UPGGKUQISSWRJJ-UHFFFAOYSA-N |
Properties
| Appearance | Light Yellow Powder |
| Antibiotic Activity Spectrum | Gram-positive bacteria; Gram-negative bacteria |
| Boiling Point | 1499.6±65.0°C at 760 mmHg |
| Melting Point | 266-266.5°C |
| Density | 1.5±0.1 g/cm3 |
| Solubility | Soluble in DMSO |
Reference Reading
1. Activation and Loading of the Starter Unit during Thiocoraline Biosynthesis
Shogo Mori, Sanjib K Shrestha, Javier Fernández, María Álvarez San Millán, Atefeh Garzan, Ahmad H Al-Mestarihi, Felipe Lombó, Sylvie Garneau-Tsodikova Biochemistry. 2017 Aug 29;56(34):4457-4467. doi: 10.1021/acs.biochem.7b00661. Epub 2017 Aug 17.
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.
2. Thiocoraline activates the Notch pathway in carcinoids and reduces tumor progression in vivo
T P Wyche, A Dammalapati, H Cho, A D Harrison, G S Kwon, H Chen, T S Bugni, R Jaskula-Sztul Cancer Gene Ther. 2014 Dec;21(12):518-25. doi: 10.1038/cgt.2014.57. Epub 2014 Nov 21.
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.
3. Thiocoraline mediates drug resistance in MCF-7 cells via PI3K/Akt/BCRP signaling pathway
Jin Jin, Yujia Zhao, Wan Guo, Bingrong Wang, Yigang Wang, Xinyuan Liu, Chuanlian Xu Cytotechnology. 2019 Feb;71(1):401-409. doi: 10.1007/s10616-019-00301-w. Epub 2019 Jan 28.
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.
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Bio Calculators
* Our calculator is based on the following equation:
Concentration (start) x Volume (start) = Concentration (final) x Volume (final)
It is commonly abbreviated as: C1V1 = C2V2
* Total Molecular Weight:
g/mol
Tip: Chemical formula is case sensitive. C22H30N4O √ c22h30n40 ╳
