Thioredoxin system modulation by plant and fungal secondary metabolites

Current Medicinal Chemistry
Fabrizio Dal PiazNunziatina De Tommasi

Abstract

Thioredoxin (Trx) is the major cellular protein disulfide reductase in a broad range of organisms, including humans. Trx, together with glutaredoxin (Grx), plays critical roles in the regulation of cellular protein redox homeostasis. Reduced thioredoxin transfers reducing equivalents to disulphides in target proteins, leading to reversible oxidation of its active centre dithiol to a disulphide. The resulting disulphide bridge is, in turn, reduced to a dithiol by thioredoxin reductase (TrxR). Increasing attention has been paid to the role of Trx, as it has been shown to be a signalling intermediate beyond its intrinsic antioxidant activity. Indeed, this protein acts as a growth factor, activates a number of transcription factors regulating cell growth and survival, acts as cofactor for ribonucleotide reductase, and promotes angiogenesis. In addition, Trx have been demonstrated to cooperatively inhibit programmed cell death. Because of the multiple roles of Trx system in tumorigenesis, this protein represents an emerging target for anti-cancer drugs. Several Trx system modulators have been identified: a semi-synthetic Trx inhibitor, PX-12 (1-methylpropyl 2-imidazolyl disulfide), has been placed in a clinical trial. However, there...Continue Reading

Citations

Dec 19, 2012·Antioxidants & Redox Signaling·Dler Faieeq Darweesh MahmoodMustapha Rouis
Jun 11, 2015·Antioxidants & Redox Signaling·Marcus CebulaElias S J Arnér
Oct 7, 2010·Molecular Plant-microbe Interactions : MPMI·Lijun SunHansong Dong
Aug 2, 2019·Cancer Chemotherapy and Pharmacology·Fariba MohammadiSeyed Isaac Hashemy
May 22, 2021·European Journal of Medicinal Chemistry·Lei ShiZhou-Rui Ma
Apr 10, 2019·Journal of Medicinal Chemistry·Mianli BianWukun Liu
Apr 24, 2018·Biomedicine & Pharmacotherapy = Biomédecine & Pharmacothérapie·Liujiu TangHaiying Ma

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