GLIOTOXIN Chemical Properties

Melting point:

221°C (rough estimate)

Boiling point:

699.7±55.0 °C(Predicted)

alpha 

D25 -290° (c = 0.08 in ethanol)

Density 

1.4069 (rough estimate)

refractive index 

1.6510 (estimate)

Flash point:

2℃

storage temp. 

2-8°C

solubility 

chloroform: 10 mg/mL, clear, colorless

form 

White solid

pka

12.90±0.40(Predicted)

color 

Monoclinic crystals from MeOH

Merck 

13,4454

BRN 

50675

Stability:

Stable for 2 yeara as supplied. Solutions in DMSO may be stored at -20°C for up to 1 month.

Safety Information

Hazard Codes 

T,Xn,F

Risk Statements 

25-36-20/21/22-11

Safety Statements 

36/37/39-45-36/37-16

RIDADR 

UN 3462 6.1/PG 3

WGK Germany 

3

RTECS 

KB4725000

F 

4.2-10-23

HazardClass 

6.1(b)

PackingGroup 

III

HS Code 

29419090

Toxicity

LD50 oral in mouse: 67mg/kg

MSDS

• Language:English Provider:SigmaAldrich

GLIOTOXIN Usage And Synthesis

Description

Gliotoxin 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).

Chemical Properties

White powder

Uses

Gliotoxin 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.

Uses

Gliotoxin is a potent epithiodioxopiperazine mycotoxin produced by species of Gliocladium, Aspergillus and Penicillium. At the cellular level gliotoxin inhibits a broad range of unrelated mechanisms, including inhibition of chymotrypsin-like activity of the 20S proteasome and Ca2+ release from mitochondria, activation of transcription factor NF-κB in response to a variety of stimuli in T and B cells, anti-inflammatory activity, and inhibition of farnesyltransferase and geranylgeranyltransferase. The mode of action appears to be via covalent interaction with proteins through mixed disulphide formation. Gliotoxin inhibits a number of thiol-requiring enzymes and also displays antioxidant and immunomodulatory activity.

Definition

ChEBI: A pyrazinoindole with a disulfide bridge spanning a dioxo-substituted pyrazine ring; mycotoxin produced by several species of fungi.

Hazard

Poison.

Biological Activity

Immunosuppressive agent; blocks phagocytosis, cytokine production and proliferation of T and B cells. Non-competitively inhibits chymotrypsin-like activity of 20S proteasome; prevents degradation of I κ B α , an endogenous blocker of NF- κ B. Also inhibits farnesyltransferase and geranylgeranyltransferase I (IC 50 values are 80 and 17 μ M respectively) and displays antitumor activity against breast cancer in vivo .

Safety Profile

Poison by intraperitoneal andintravenous routes. When heated to decomposition itemits very toxic fumes such as SOx and NOx.

target

COX | Wnt/β-catenin | Antifection

storage

-20°C (desiccate)

Purification Methods

Purify gliotoxin by recrystallisation from MeOH. Its solubility in CHCl3 is 1%. The dibenzoyl derivative has m 202o (from CHCl3/MeOH). [Glister & Williams Nature 153 651 1944, Elvidge & Spring J Chem Soc Suppl 135 1949, Johnson et al. J Am Chem Soc 65 2005 1943, Bracken & Raistrick Biochem J 41 569 1947.]

References

Waring & Beaver (1996), Gliotoxin and related epipolythiodioxopiperazines; Gen. Pharmacol., 27 1311 Kroll et al. (1999), The secondary fungal metabolite gliotoxin targets proteolytic activities of the proteasome; Chem. Biol., 6 689 Fitzpatrick et al. (2000), In vitro and in vivo effects of gliotoxin, a fungal metabolite: efficacy against dextran sodium sulfate-induced colitis in rats; Dig. Dis. Sci., 45 2327 Konig et al. (2019), Gliotoxin from Aspergillus fumigatus Abrogates Leukotriene B4 Formation through Inhibition of Leukotriene A4 Hydrolase ; Cell Chem. Biol., 26 524 Hubmann et al. (2020), Targeting Nuclear NOTCH2 by Gliotoxin Recovers a Tumor-Suppressor NOTCH3 Activity in CLL; Cells, 9 1484

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