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.

[8] Gliotoxin contributes to the pathogenicity of opportunistic fungi by suppressing the immune system response of its host.

However, afterwards Weindling reported that the fungus had been misidentified based on the advice of C. Thom and M. Timonin, and that the compound instead was isolated from Gliocladium finbriatum.

Gliotoxin possesses immunosuppressive properties that may suppress and cause apoptosis in certain cells of the immune system, including neutrophils, eosinophils, granulocytes, macrophages, and thymocytes.

[14] Specifically, neutrophils exposed to gliotoxin release less reactive oxygen species (ROS) and complete fewer phagocytic activities.

[14] Gliotoxin inactivates many different enzymes, including nuclear factor-κB (NF-κB), NADPH oxidase, and glutaredoxin.

Interactions occur between sulfur molecules that make up the disulfide bridge and thiol groups contained in cysteine residues.

This intracellular gliotoxin activates the transcription factor GliZ, facilitating gli gene cluster expression, and an enzyme called GtmA (S-adenosylmethionine (SAM)-dependent bis-thiomethyltransferase).

[19] A Michael reaction of 4-carbo-tert-butoxybenzene oxide 2 in excess in a solvent of dimethyl sulfoxide (DMSO) containing Triton B at room temperature produced the alcohol 3 in 88% overall yield.

It is expected that there would be a trans-opening of the epoxide ring for 2, so the resulting epimers would differ in the relative configuration of the thioacetal bridge and the alcoholic group depending on the orientation of compounds 1 and 2 in the transition state.

Adding phenyllithium slowly to a mixture of 6 and chloromethyl benzyl ether in excess in THF at 78 °C gave the benzylgliotoxin adduct 7 at 45% yield.

Spectroscopic analysis (NMR, ir, uv, MS) and TLC comparison showed that the synthetic substance was identical to natural gliotoxin.

Individuals taking immunosuppressive medications or with previous or current exposure to chemotherapy radiation are at higher risk for the development of these tumors.

[22] Gliotoxin is toxic if swallowed or inhaled, and can cause skin and eye irritation if exposure occurs to these areas.

[18] GipA is a transcriptional regulator for the expression of the GliA transporter protein, which is required for gliotoxin secretion.

[18] Low-dose gliotoxin can exert antioxidant activities in the presence of the thioredoxin redox system that can counter the release of ROS in cells as a result of the electron transport chain (ETC) during cellular respiration.

[18] Doses of gliotoxin less than 40 nM can also activate latent HIV-1 gene expression, serving as a diagnostic of HIV infection.

Treatment of 20 nM gliotoxin reversed HIV-1 latency without interfering in the activation of CD4+ or CD8+ T-cells that are involved in the elimination of HIV-infected cells.