Gliotoxin

Gliotoxin
IUPAC name (3R,6S,10aR)-6-hydroxy-3-(hydroxymethyl)-2-methyl-2,3,6,10-tetrahydro-5aH-3,10a-epidithiopyrazino[1,2-a]indole-1,4-dione
Identifiers
CAS number	67-99-2 Y
PubChem	6223
ChemSpider	5988 Y
ChEMBL	CHEMBL331627 Y, CHEMBL145588
Jmol-3D images	{{#if:O=C1N([C@@]2(SS[C@@]14N(C2=O)[C@H]3C(=C\C=C/[C@@H]3O)/C4)CO)C|Image 1
SMILES O=C1N([C@@]2(SS[C@@]14N(C2=O)[C@H]3C(=C\C=C/[C@@H]3O)/C4)CO)C
InChI InChI=1S/C13H14N2O4S2/c1-14-10(18)12-5-7-3-2-4-8(17)9(7)15(12)11(19)13(14,6-16)21-20-12/h2-4,8-9,16-17H,5-6H2,1H3/t8-,9-,12+,13+/m0/s1 Y Key: FIVPIPIDMRVLAY-RBJBARPLSA-N Y
Properties
Molecular formula	C13H14N2O4S2
Molar mass	326.4 g/mol
Appearance	white to light yellow solid
Density	1.75 g/ml
Solubility in DMSO	soluble
Hazards
MSDS	MSDS from Fermentek
Y (verify) (what is: Y/N?) Except where noted otherwise, data are given for materials in their standard state (at 25 °C (77 °F), 100 kPa)
Infobox references

Gliotoxin is a sulfur-containing mycotoxin produced by several species of fungi, including pathogens of humans such as Aspergillus fumigatus,^[1] and also by species of Trichoderma, and Penicillium. Gliotoxin has also been reported from yeasts of the genus Candida,^[2] but results from other studies have cast doubt on the production of this metabolite by Candida fungi.^[3][4] Gliotoxin was originally isolated from Gliocladium fimbriatum, and was named accordingly. It is an epipolythiodioxopiperazine metabolite.

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. It noncompetitively inhibits the chymotrypsin-like activity of the 20S proteasome. In vivo it displays anti-inflammatory activity.^[5] It acts by blocking thiol groups in the cell membranes. It was investigated as an antibiotic and antifungal in the 1940s and recently as an antiviral agent.^[6][7]

Biosynthesis

References

1. ↑ Scharf DH, Heinekamp T, Remme N, Hortschansky P, Brakhage AA, Hertweck C. (2012). "Biosynthesis and function of gliotoxin in Aspergillus fumigatus". Appl Microbiol Biotechnol. 93: 467–72. doi:10.1007/s00253-011-3689-1. PMID 22094977. 
2. ↑ Larsen, B,Shah, D, 1991 "Candida isolates of yeast produce a gliotoxin-like substance" Mycopathologia 116:203-208, 1991.
3. ↑ Kupfahl C, Ruppert T, Dietz A, Geginat G, Hof H. (2007). "Candida species fail to produce the immunosuppressive secondary metabolite gliotoxin in vitro". FEMS Yeast Res 7 (6): 986–92. doi:10.1111/j.1567-1364.2007.00256.x. PMID 17537180. 
4. ↑ Kosalec I, Puel O, Delaforge M, Kopjar N, Antolovic R, Jelic D, Matica B, Galtier P, Pepeljnjak S. (2010). "Isolation and cytotoxicity of low-molecular-weight metabolites of Candida albicans". Front Biosci 13: 6893–904. doi:10.2741/3197. PMID 18508703. 
5. ↑ http://www.biomol.com/SiteData/docs/productdata/pi129.pdf
6. ↑ Herrick, J. Arthur (March 1945), "Effects of Gliotoxin on Trichophyton Gypseum", The Ohio Journal of Science 
7. ↑ McDougall, J. K. (March 02, 2005), "Antiviral action of gliotoxin", Archives of Virology 

• Identification of an agent in cultures of Aspergillus fumigatus displaying anti-phagocytic and immunomodulating activity in vitro: A. Müllbacher, et al.; J. Gen. Microbiol. 131, 1251 (1985)

• Clinical Isolates of yeast produce a gliotoxin-like substance". D. Shah and B. Larsen; Mycopatholgia 116: 203-208,(1991)

• "Mechanism of gliotoxin action and factors mediating gliotoxin sensitivity". R.W. Jones & J.G. Hancock; J. Gen. Microbiol. 134: 2067-2075 (1988)

• Gliotoxin stimulates Ca²⁺ release from intact rat liver mitochondria: M. Schweizer & C. Richter; Biochemistry 33, 13401 (1994)

• Extracellular calcium is not required for gliotoxin or dexamethasone- induced DNA fragmentation: a reappraisal of the use of EGTA: P. Waring & A. Sjaarda; Int. J. Immunopharmacol. 17, 403 (1995)

External links

Puri, A., Ahmad, A. and Panda, B. P. (2010), Development of an HPTLC-based diagnostic method for invasive aspergillosis. Biomed. Chromatogr., 24: 887–892. doi: 10.1002/bmc.1382

Gliotoxin product page from Fermentek