The Multiple Properties of Gliotoxin and Other Epipolythiodioxopiperazine Metabolites

Abstract

The bridged disulfide ring of the fungal metabolite gliotoxin presents both synthetic challenges and confers the molecule with a variety of interesting biological activities. This review summarises recent synthetic strategies used to insert the disulfide and polysulfide bridge across the diketopiperazine ring and briefly describes the limited structure–activity data available for this class of molecule which clearly shows the presence of the disulfide bridge dominates their biological activities. The review also covers possible cellular targets of these toxins, the possible role for the disulfide bridge in toxicity and cellular uptake mechanisms, and the nature of the cell death induced by the epipolythiopiperazinedione toxins. The potential role of this simple molecule as a diagnostic marker for invasive aspergillosis is also discussed.