Epipolythiodioxopiperazines: From Chemical Architectures to Biological Activities and Ecological Significance—A Comprehensive Review

Epipolythiodioxopiperazines (ETPs), characterized by a diketopiperazine (DKP) core bridged by disulfide or polysulfide bonds, exhibit exceptional structural diversity and functional adaptability. This review comprehensively explores their multifaceted properties, covering chemical structural characteristics, therapeutic application potential, and ecological functional value. Structural diversity arises from variations in the core DKP scaffold, sulfur bridge connectivity patterns, and additional modifications. Biosynthesis involves initial DKP assembly, enzyme-catalyzed sulfur incorporation and oxidation to form the signature sulfur bridge of ETPs, diversification by tailoring enzymes, and distinct regulatory mechanisms. ETPs possess diverse biological activities, including cytotoxicity, antitumor activity, antimicrobial properties, and immunomodulatory functions. From an ecological standpoint, ETPs mediate fungal–host interactions and influence competition and symbiosis within fungal communities. Furthermore, this review also addresses the current challenges and outlines future research directions. In summary, as a class of significant compounds spanning the fields of chemistry, biology, medicine, and ecology, ETPs deserve focused attention for their research value and application prospects.