Gliotoxin

Gliotoxin
Skeletal formula of gliotoxin
Space-filling model of the gliotoxin molecule
Names
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
67-99-2 YesY
3D model (Jmol) Interactive image
ChEMBL ChEMBL331627 YesY
ChEMBL145588 N
ChemSpider 5988 YesY
ECHA InfoCard 100.163.992
PubChem 6223
Properties
C13H14N2O4S2
Molar mass 326.4 g/mol
Appearance white to light yellow solid
Density 1.75 g/ml
Solubility in DMSO soluble
Hazards
Safety data sheet MSDS from Fermentek
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).
N verify (what is YesYN ?)
Infobox references

Gliotoxin is a sulfur-containing mycotoxin that belongs to a class of naturally occurring 2,5-diketopiperazines[1] produced by several species of fungi, especially those of marine origin. It is the most prominent member of the epipolythiopiperazines, a large class of natural products featuring a diketopiperazine with di- or polysulfide linkage. These highly bioactive compounds have been the subject of numerous studies aimed at new therapeutics.[2] Gliotoxin was originally isolated from Gliocladium fimbriatum, and was named accordingly. It is an epipolythiodioxopiperazine metabolite.

Occurrence

The compound is produced by human pathogens such as Aspergillus fumigatus,[3] and also by species of Trichoderma, and Penicillium. Gliotoxin has also been reported from yeasts of the genus Candida,[4] but results from other studies have cast doubt on the production of this metabolite by Candida fungi.[5][6]

Mechanism of action

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. 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.[7]

References

  1. ↑ Borthwick AD (2012). "2,5-Diketopiperazines: Synthesis, Reactions, Medicinal Chemistry, and Bioactive Natural Products". Chemical Reviews. 112 (7): 3641–3716. doi:10.1021/cr200398y. PMID 22575049.
  2. ↑ Jiang, C.-S.; Muller, W. E. G.; Schroder, H. C.; Guo, Y.-W., "Disulfide- and Multisulfide-Containing Metabolites from Marine Organisms", Chem. Rev. 2012, 112, 2179-2207. doi:10.1021/cr200173z
  3. ↑ 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.
  4. ↑ Larsen, B,Shah, D, 1991 "Candida isolates of yeast produce a gliotoxin-like substance" Mycopathologia 116:203-208, 1991.
  5. ↑ 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.
  6. ↑ 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.
  7. ↑ McDougall, J. K. (March 2, 2005), "Antiviral action of gliotoxin", Archives of Virology

Further reading

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