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Glutathione and glutathione disulfide – their biomedical and pharmaceutical applications

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Abstract

Glutathione (GSH) is an endogenous tripeptide (Glu-Cys-Gly) and the most abundant endogenous antioxidant. It protects the body against oxidative stress and reactive electrophiles. GSH and its oxidized form glutathione disulfide (GSSG) make up the most important thiol redox buffer in the body, and its homeostasis is critical to many important cellular functions. Dysfunction or disruption of the redox buffer has been implicated in various diseases and the implications make GSH, GSSG, and their related systems valid and effective targets for medicinal chemistry interventions. For example, increased levels of GSH and GSH related systems in cancer have been employed as a basis for anticancer prodrug activation, anticancer drug delivery and anticancer drug development. The enriched GSH transporters in the blood brain barrier has been effectively employed for the design of brain targeting prodrugs and brain drug delivery systems. Further, a glutathione conjugate can serve as a marker for the presence of a reactive electrophile providing valid information for the evaluation of a drug candidate. This review focuses on GSH/GSSG system-based biomedical and pharmaceutical applications with relevant basic and comprehensive background information.

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    Guan, X. Glutathione and glutathione disulfide – their biomedical and pharmaceutical applications. Med Chem Res 32, 1972–1994 (2023). https://doi.org/10.1007/s00044-023-03116-9

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