salicylates and Hyperoxaluria--Primary

Primary hyperoxaluria type 1 (PH1) is a rare life-threatening genetic disease related to glyoxylate metabolism and characterized by accumulation of calcium oxalate crystals. Current therapies involve hepatic and/or renal transplantation, procedures that have significant morbidity and mortality and require long-term immunosuppression. Thus, a pharmacological treatment is urgently needed. We introduce here an unprecedented activity of salicylic acid derivatives as agents capable of decreasing oxalate output in hyperoxaluric hepatocytes at the low micromolar range, which means a potential use in the treatment of PH1. Though correlation of this phenotypic activity with glycolate oxidase (GO) inhibition is still to be verified, most of the salicylic acids described here are GO inhibitors with IC

Topics: Alcohol Oxidoreductases; Animals; Cells, Cultured; Computer Simulation; Drug Design; Hepatocytes; Humans; Hyperoxaluria, Primary; Male; Mice, Inbred C57BL; Mice, Mutant Strains; Molecular Docking Simulation; Oxalates; Salicylates; Structure-Activity Relationship; Transaminases