Gliotoxin

Names

[ CAS No. ]:
67-99-2

[ Name ]:
Gliotoxin

[Synonym ]:
(1R,7S,8S,11R)-7-Hydroxy-11-(hydroxymethyl)-15-methyl-12,13-dithia-9,15-diazatetracyclo[9.2.2.0.0]pentadeca-3,5-diene-10,14-dione
epithiodiketopiperazine
Gliotoxin,(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
MFCD00058534
(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-dione
[3R-(3a,5ab,6b,10aa)]-2,3,5a,6-Tetrahydro-6-hydroxy-3-(hydroxymethyl)-2-methyl-10H3,10a-epidithiopyrazino[1,2-a]indole-1,4-dione
10H-3,10a-(Iminomethano)[1,2,4]dithiazino[4,3-a]indole-4,11(3H)-dione, 5a,6-dihydro-6-hydroxy-3-(hydroxymethyl)-12-methyl-, (3R,5aS,6S,10aR)-
Gliotoxin

Biological Activity

[Description]:

Gliotoxin is a secondary metabolite, the most abundant mycotoxin secreted by A. fumigatus, inhibits the phagocytosis of macrophages and the immune functions of other immune cells [1]. Gliotoxin inhibits inducible NF-κB activity by preventing IκB degradation, which consequently induces host-cell apoptosis[2]. Gliotoxin activates PKA and increases intracellular cAMP concentration; modulates actin cytoskeleton rearrangement to facilitate A. fumigatus internalization into lung epithelial cells[3].

[Related Catalog]:

Signaling Pathways >> Apoptosis >> Apoptosis

Signaling Pathways >> Protein Tyrosine Kinase/RTK >> PKA

Signaling Pathways >> Stem Cell/Wnt >> PKA

Research Areas >> Inflammation/Immunology

[References]

[1]. Schlam D, et al. Gliotoxin Suppresses Macrophage Immune Function by Subverting Phosphatidylinositol 3,4,5-Trisphosphate Homeostasis. MBio. 2016 Apr 5;7(2):e02242.

[2]. Coméra C, et al. Gliotoxin from Aspergillus fumigatus affects phagocytosis and the organization of the actin cytoskeleton by distinct signalling pathways in human neutrophils. Microbes Infect. 2007 Jan;9(1):47-54. Epub 2006 Dec 12.

[3]. Zhang C, et al. Gliotoxin Induces Cofilin Phosphorylation to Promote Actin Cytoskeleton Dynamics and Internalization of Aspergillus fumigatus Into Type II Human Pneumocyte Cells. Front Microbiol. 2019 Jun 18;10:1345.

Chemical & Physical Properties

[ Density]:
1.8±0.1 g/cm3

[ Boiling Point ]:
699.7±55.0 °C at 760 mmHg

[ Melting Point ]:
153.5ºC

[ Molecular Formula ]:
C₁₃H₁₄N₂O₄S₂

[ Molecular Weight ]:
326.391

[ Flash Point ]:
377.0±31.5 °C

[ Exact Mass ]:
326.039490

[ PSA ]:
131.68000

[ LogP ]:
0.52

[ Vapour Pressure ]:
0.0±5.0 mmHg at 25°C

[ Index of Refraction ]:
1.814

Toxicological Information

CHEMICAL IDENTIFICATION

RTECS NUMBER :: KB4725000

CHEMICAL NAME :: 10H-3,10a-Epidithiopyrazino(1,2-a)indole-1,4-dione, 2,3,5a,6-hydroxy-3- (hydroxymethyl)-2-methyl-, (3R-(3-alpha,5a-beta,6-beta,10a-alpha))-

CAS REGISTRY NUMBER :: 67-99-2

BEILSTEIN REFERENCE NO. :: 0050675

LAST UPDATED :: 199709

DATA ITEMS CITED :: 9

MOLECULAR FORMULA :: C13-H14-N2-O4-S2

MOLECULAR WEIGHT :: 326.41

WISWESSER LINE NOTATION :: T C6 B566/JO A 2BJ O AVN JXSS NNV EU GU MHTT&&J DQ M1Q N

HEALTH HAZARD DATA

ACUTE TOXICITY DATA

TYPE OF TEST :: LDLo - Lowest published lethal dose

ROUTE OF EXPOSURE :: Intravenous

SPECIES OBSERVED :: Rodent - rat

DOSE/DURATION :: 45 mg/kg

TOXIC EFFECTS :: Details of toxic effects not reported other than lethal dose value

TYPE OF TEST :: LDLo - Lowest published lethal dose

ROUTE OF EXPOSURE :: Unreported

SPECIES OBSERVED :: Rodent - rat

DOSE/DURATION :: 50 mg/kg

TOXIC EFFECTS :: Behavioral - altered sleep time (including change in righting reflex)

TYPE OF TEST :: LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :: Oral

SPECIES OBSERVED :: Rodent - mouse

DOSE/DURATION :: 67 mg/kg

TOXIC EFFECTS :: Details of toxic effects not reported other than lethal dose value

TYPE OF TEST :: LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :: Intraperitoneal

SPECIES OBSERVED :: Rodent - mouse

DOSE/DURATION :: 32 mg/kg

TOXIC EFFECTS :: Details of toxic effects not reported other than lethal dose value

TYPE OF TEST :: LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :: Subcutaneous

SPECIES OBSERVED :: Rodent - mouse

DOSE/DURATION :: 25 mg/kg

TOXIC EFFECTS :: Details of toxic effects not reported other than lethal dose value

TYPE OF TEST :: LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :: Intravenous

SPECIES OBSERVED :: Rodent - mouse

DOSE/DURATION :: 7800 ug/kg

TOXIC EFFECTS :: Details of toxic effects not reported other than lethal dose value

TYPE OF TEST :: LDLo - Lowest published lethal dose

ROUTE OF EXPOSURE :: Intravenous

SPECIES OBSERVED :: Rodent - rabbit

DOSE/DURATION :: 45 mg/kg

TOXIC EFFECTS :: Vascular - BP lowering not characterized in autonomic section Gastrointestinal - hypermotility, diarrhea

TYPE OF TEST :: LDLo - Lowest published lethal dose

ROUTE OF EXPOSURE :: Oral

SPECIES OBSERVED :: Rodent - hamster

DOSE/DURATION :: 25 mg/kg

TOXIC EFFECTS :: Details of toxic effects not reported other than lethal dose value

MUTATION DATA

TYPE OF TEST :: DNA repair

TEST SYSTEM :: Bacteria - Bacillus subtilis

DOSE/DURATION :: 250 mg/L

REFERENCE :: MYCPAH Mycopathologia. (Kluwer Academic Pub. Group, Distribution Centre, POB 322, 3300 AH Dordrecht, Netherlands) V.1- 1938- Volume(issue)/page/year: 87,43,1984

Safety Information

[ Symbol ]:

GHS02, GHS07

[ Signal Word ]:
Danger

[ Hazard Statements ]:
H225-H302-H312-H319-H332

[ Precautionary Statements ]:
P210-P280-P305 + P351 + P338

[ Personal Protective Equipment ]:
Eyeshields;Faceshields;Gloves;type P2 (EN 143) respirator cartridges

[ Hazard Codes ]:
T

[ Risk Phrases ]:
25

[ Safety Phrases ]:
S45;S36/S37/S39

[ RIDADR ]:
UN 3462 6.1/PG 3

[ WGK Germany ]:
3

[ RTECS ]:
KB4725000

[ Packaging Group ]:
III

[ Hazard Class ]:
6.1(b)

[ HS Code ]:
29419090

Synthetic Route

Click to get detail synthetic route

Precursor & DownStream

Precursor

DownStream

Articles

The MAP kinase MpkA controls cell wall integrity, oxidative stress response, gliotoxin production and iron adaptation in Aspergillus fumigatus.

Mol. Microbiol. 82(1) , 39-53, (2011)

The saprophytic fungus Aspergillus fumigatus is the most important air-borne fungal pathogen. The cell wall of A. fumigatus has been studied intensively as a potential target for development of effect...

Single-pot derivatisation strategy for enhanced gliotoxin detection by HPLC and MALDI-ToF mass spectrometry.

Anal. Bioanal. Chem 401(8) , 2519-29, (2011)

Gliotoxin is produced by non-ribosomal peptide synthesis and secreted from certain fungi, including Aspergillus fumigatus. It is an epipolythiodioxopiperazine that contains an intact disulphide bridge...

Individual and combined effects of mycotoxins from typical indoor moulds.

Toxicol. In Vitro 27(6) , 1970-8, (2013)

The mycotoxins patulin, gliotoxin and sterigmatocystin can be produced by common indoor moulds and enter the human body via inhalation of mycotoxin containing spores and particulates. There are variou...