Basic information
- CAS
67-99-2- Standard SMILES
CN1C(=O)[C@]23CC4=CC=C[C@H](O)[C@H]4N2C(=O)[C@@]1(CO)SS3- InChIKey
FIVPIPIDMRVLAY-RBJBARPLSA-N- Molecular formula
- C13H14N2O4S2
- Average molar mass
- 326.4 g/mol
- Monoisotopic mass
- 326.03949928
Overview
Gliotoxin is a pyrazinoindole with a disulfide bridge spanning a dioxo-substituted pyrazine ring; mycotoxin produced by several species of fungi. It has a role as a mycotoxin, an immunosuppressive agent, an antifungal agent, a proteasome inhibitor and an EC 2.5.1.58 (protein farnesyltransferase) inhibitor. It is an organic disulfide, an organic heterotetracyclic compound, a dipeptide and a pyrazinoindole.
Names & identifiers
- Preferred name
- Gliotoxin
- IUPAC
- (1R,7S,8S,11R)-7-hydroxy-11-(hydroxymethyl)-15-methyl-12,13-dithia-9,15-diazatetracyclo[9.2.2.01,9.03,8]pentadeca-3,5-diene-10,14-dione
- English name
- GLIOTOXIN
- Molecular formula
- C13H14N2O4S2
- Molecular weight
- 326.39
Names & synonyms
gliotoxin67-99-2AspergillinDTXSID608771795L648PH06KCHEBI:5385NSC-10286610H-3,10a-Epidithiopyrazino(1,2-a)indole-1,4-dione, 2,3,5a,6-tetrahydro-6-hydroxy-3-(hydroxymethyl)-2-methyl-GliotoxinsS. N.-12870(3R,5aS,6S,10aR)-6-hydroxy-3-(hydroxymethyl)-2-methyl-2,3,6,10-tetrahydro-5aH-3,10a-epidithiopyrazino[1,2-a]indole-1,4-dioneNSC102866
Show more names
S-82s.n.12870Aids086418Aids-086418Gliotoxin solutionAspergillin solutionGliotoxin in Acetonitrile
(3R,5aS,6S,10aR)-2,3,5a,6-Tetrahydro-6-hydroxy-3-(hydroxymethyl)-2-methyl-10H-3,10a-epidithiopyrazino[1,2-a]indole-1,4-dione10H-3,10A-EPIDITHIOPYRAZINO(1,2-A)INDOLE-1,4-DIONE, 2,3,5A,6-TETRAHYDRO-6-HYDROXY-3-(HYDROXYMETHYL)-2-METHYL-, (3R,5AS,6S,10AR)-(3R,5aS,6S,10aR)-2,3,5a,6-Tetrahydro-6-hydroxy-3-(hydroxymethyl)-2-methyl-10H-3,10a-epidithiopyrazino(1,2-a)indole-1,4-dione(3R,5aS,6S,10aR)-6-hydroxy-3-(hydroxymethyl)-2-methyl-2,3,6,10-tetrahydro-5aH-3,10a-epidithiopyrazino(1,2-a)indole-1,4-dioneRefChem:143379DTXCID7010152617-hydroxy-11-(hydroxymethyl)-15-methyl-12,13-dithia-9,15-diazatetracyclo(9.2.2.01,9.03,8)pentadeca-3,5-diene-10,14-dioneGliotoxin from Gliocladium fimbriatum
Properties
Computed structural properties
- XLogP
- -0.7
- Topological polar surface area
- 132 Ų
- Hydrogen bond donors
- 2
- Hydrogen bond acceptors
- 6
- Rotatable bonds
- 1
- Heavy atoms
- 21
- Formal charge
- 0
- Complexity
- 621
Experimental & physicochemical properties
DrugsPharmaceuticals -> Antibiotics
Physicochemical properties
- Melting point
- 221 °C · 221°C (rough estimate)
- Boiling point
- 699.7 · 699.7±55.0 °C(Predicted)
- alpha
- 25 · D25 -290° (c = 0.08 in ethanol)
- Density
- 1.4069 · 1.4069 (rough estimate)
- refractive index
- 1.651 · 1.6510 (estimate)
- Flash point
- 2 ℃ · 2℃
- storage temp.
- 2 · 2-8°C
- solubility
- 10 mg/mL, · chloroform: 10 mg/mL, clear, colorless
- form
- White solid
- pka
- 12.9 · 12.90±0.40(Predicted)
- color
- Monoclinic crystals from MeOH
- Merck
- 13 · 13,4454
- BRN
- 50675 · 50675
Safety & regulation
Safety information is for reference only and does not replace the supplier’s Safety Data Sheet (SDS), applicable regulations, or professional assessment.
GHS classification
GHS Classification
Danger
H301 (100%): Toxic if swallowed [Danger Acute toxicity, oral]
P264, P270, P301+P316, P321, P330, P405, and P501 (click each P-code to see the statement)
Aggregated GHS information provided per 42 reports by companies from 1 notifications to the ECHA C&L Inventory.
Hazard information
Regulatory Information10H-3,10a-Epidithiopyrazino1,2-aindole-1,4-dione, 2,3,5a,6-tetrahydro-6-hydroxy-3-(hydroxymethyl)-2-methyl-, (3R,5aS,6S,10aR)-: Does not have an individual approval but may be used under an appropriate group standard
Hazard Classes and CategoriesAcute Tox. 3 (100%)
Toxicology
Health EffectsGliotoxin has immunosuppressive effects. It is also cytotoxic and causes neurite degeneration. (L1941, A2951)
Exposure RoutesOral, dermal, inhalation, and parenteral (contaminated drugs). (A3101)
Toxicity Summary
Gliotoxin possesses immunosuppressive properties as it may suppress and cause apoptosis in certain types of cells of the immune system, including neutrophils, eosinophils, granulocytes, macrophages, and thymocytes. It also acts as an inhibitor of farnesyl transferase. Gliotoxin noncompetitively inhibits the chymotrypsin-like activity of the 20S proteasome and displays anti-inflammatory activity. It acts by blocking thiol groups in the cell membranes. Gliotoxin is also cytotoxic and causes neurite degeneration. Mycotoxins are often able to enter the liver and kidney by human organic anion transporters (hOATs) and human organic cation transporters (hOCTs). They can also inhibit uptake of anions and cations by these transporters, interefering with the secretion of endogenous metabolites, drugs, and xenobiotics including themselves. This results in increased cellular accumulation of toxic compounds causing nephro- and hepatotoxicity. (L1941, A2951, A3014)
Chemistry & industry
Pharmacology
MeSH Pharmacological Classification
Agents that suppress immune function by one of several mechanisms of action. Classical cytotoxic immunosuppressants act by inhibiting DNA synthesis. Others may act through activation of T-CELLS or by inhibiting the activation of HELPER CELLS. While immunosuppression has been brought about in the past primarily to prevent rejection of transplanted organs, new applications involving mediation of the effects of INTERLEUKINS and other CYTOKINES are emerging.
Uses & manufacturing
Uses
Gliotoxin is a sulfur-containing antibiotic produced by several species of fungi, some of which are pathogens of humans such as Aspergillus, and also by species of Trichoderma, and Penicillium. Gliotoxin possesses immunosuppressive properties. (L1941)
Applications
DescriptionGliotoxin is an immunosuppressive mycotoxin produced by pathogenic strains of Aspergillus and other fungi with diverse biological activities. It inhibits 20S proteasomal chymotrypsin activity (IC50 = 10 μM), blocking the degradation of IκBα and preventing the activation of NF-κB. Gliotoxin induces apoptosis in monocytes and dendritic cells and reduces phagocytosis by neutrophils. It suppresses viral infection by Nipah and Hendra virus in HEK293T cells (IC50s = 149 and 579 nM, respectively). Under reducing conditions, gliotoxin inhibits leukotriene A4 hydrolase (LTA4H; ) epoxide hydrolase activity, but not aminopeptidase activity, and leukotriene B4 (LTB4; ) synthesis in neutrophils and monocytes. In vivo, gliotoxin (5 mg/kg) reduces LTB4 plasma levels and blocks peritoneal neutrophil infiltration in a mouse model of peritonitis induced by zymosan A . It also inhibits geranylgeranyltransferase I and farnesyltransferase (IC50s = 17 and 80 μM, respectively).
UsesGliotoxin is a sulfur-containing mycotoxin produced by species of fungi and pathogens of humans. Gliotoxin exhibits inhibitory activities against histone H3K9 methyltransferase, a key enzyme in the re gulation of transcriptional activity by writing epigenetic marks. Gliotoxin also exhibits immunosuppressive properties by causing apoptosis of cells of the immune system. In addition, various studies suggests Gliotoxin may also be a potential anti-inflammatory, antibiotic, antifungal and antiviral agent.
Related reactions
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Compound notes
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