The design of redox active thiol peroxidase mimics: Dihydrolipoic acid recognition correlates with cytotoxicity and prooxidant action

Biochemical Pharmacology
B ZadehvakiliGregory I Giles

Abstract

Redox active molecules containing organoselenium or organotellurium groups catalyse the oxidation of cellular thiols by hydrogen peroxide and are currently being developed as therapeutic agents. Potentially these synthetic thiol peroxidase (TPx) mimics can protect cells from oxidative stress by catalysing the reduction of reactive oxygen species by the cellular thiol glutathione, an activity which mimics the function of the antioxidant enzyme glutathione peroxidase. Alternatively they can act as prooxidants by catalysing the oxidation of essential thiol species within the cell. However the structure-activity relationships which determine the choice of thiol substrate, and hence the overall antioxidant or prooxidant outcome of drug administration, remain unknown. We report the first study that relates the pharmacological properties of TPx mimics with their solubility and catalytic activity using different thiol substrates. We used a series of structurally related compounds PhMCnH2n+1 (M=Se, Te; n=4-7) and investigated their ability to catalyse the oxidation of the cellular thiols glutathione and dihydrolipoic acid by hydrogen peroxide. The resulting rate constants (kobs) were then related to compound cytotoxicity and antioxidant...Continue Reading

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Citations

Jun 23, 2016·Data in Brief·B ZadehvakiliG I Giles
Oct 15, 2013·Trends in Biochemical Sciences·Ryan J MaillouxMary-Ellen Harper
Feb 4, 2014·European Journal of Pharmacology·Shimaa M ElshazlyWaleed Barakat
May 31, 2021·Bioorganic & Medicinal Chemistry Letters·Andrea AngeliClaudiu T Supuran

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