Resumen de Biotransformation of Phenazine 5,10-Dioxides under Hypoxic Conditions as an Example of Activation of Anticancer Prodrug: An Interdisciplinary Experiment for Biochemistry or Organic Chemistry
María Laura Lavaggi, Mauricio Cabrera, Laura Celano, Leonor Thomson, Hugo Cerecetto, Mercedes González
The goal of this work was to include an interdisciplinary research-oriented laboratory experiment taken from medicinal chemistry into the undergraduate biochemistry or organic studies. Phenazine 5,10-dioxides with selective cytotoxicity under hypoxia and with relevance in solid tumor treatment were selected to simulate different metabolism states. In this laboratory experiment, metabolism of 7-bromo-2-hydroxyphenazine-5,10-dioxide under simulated hypoxia and normoxia was studied using rat liver cytosol. Differential hypoxic and normoxic metabolism were monitored by thin-layer chromatography. Specific enzyme inhibitors, dicoumarol, ketoconazole, and menadione, were employed to identify the enzymatic system involved. This experiment introduced students to the concept of drug metabolism, activation, and mechanism of action. Furthermore, basic biochemical techniques of enzyme isolation and study were also discussed.
