Repozytorium publikacji - Politechnika Gdańska

Here, we report the metabolic profile and the results of associated metabolic studies of 2-hydroxyacridinone (2-OH-AC), the reference compound for antitumor-active imidazo- and triazoloacridinones. Electrochemistry coupled with mass spectrometry was applied to simulate the general oxidative metabolism of 2-OH-AC for the first time. The reactivity of 2-OH-AC products to biomolecules was also examined. The usefulness of the electrochemistry for studying the reactive drug metabolite trapping (conjugation reactions) was evaluated by the comparison with conventional electrochemical (controlled-potential electrolysis) and enzymatic (microsomal incubation) approaches. 2-OH-AC oxidation products were generated in an electrochemical thin-layer cell. Their tentative structures were assigned based on tandem mass spectrometry in combination with accurate mass measurements. Moreover, the electrochemical conversion of 2-OH-AC in the presence of reduced glutathione and/or N-acetylcysteine unveiled the formation of reactive metabolite-nucleophilic trapping agent conjugates (m/z 517 and m/z 373, respectively) via the thiol group. This glutathione S-conjugate was also identified after electrolysis experiment as well as was detected in liver microsomes. Summing up, the present work illustrates that the electrochemical simulation of metabolic reactions successfully supports the results of classical electrochemical and enzymatic studies. Therefore, it can be a useful tool for synthesis of drug metabolites, including reactive metabolites.

Autorzy

• dr hab. inż. Agnieszka Potęga link otwiera się w nowej karcie ,
• dr inż. Dorota Garwolińska link otwiera się w nowej karcie ,
• Anna M. Nowicka,
• dr Michał Fau,
• prof. dr hab. inż. Agata Kot-Wasik link otwiera się w nowej karcie ,
• prof. dr hab. inż. Zofia Mazerska link otwiera się w nowej karcie