Redox sensitive epidithiodioxopiperazines in biological mechanisms of toxicity

Epidithiodioxopiperazines (ETPs) are a class of secondary metabolites characterized by a bridged disulfide linkage across the alpha,alpha'-positions of the dioxopiperazine ring. This class of compounds displays a range of biological activities, attributed to the sulfur moiety in the oxidized disulfide form and/or the reduced dithiol form. The underlying mechanisms of toxicity of the ETP metabolites are still a matter of debate and this review presents an overview of the evidence for the possible pathways of toxicity.