Thiopurine Biotransformation and Pharmacological Effects: Contribution of Oxidative Stress

Thiopurine antimetabolites are important agents for the treatment of severe diseases, such as acute lymphoblastic leukemia and inflammatory bowel disease. Their pharmacological actions depend on biotransformation into active thioguanine-nucleotides; intracellular metabolism is mediated by enzymes of the salvage pathway of nucleotide synthesis and relies on polymorphic enzymes involved in thiopurines' catabolism such as thiopurine-S-methyl transferase. Given the enzymes involved in thiopurines' metabolism, it is reasonable to hypothesize that these drugs are able to induce significant oxidative stress conditions, possibly altering their pharmacological activity.