Similarity between enzymatic and electrochemical oxidation of 2-hydroxyacridinone, the reference compound of antitumor imidazoacridinones

• Autorzy: Mazerska Z.
• Języki publikacji: EN

Abstrakty

EN

The present work is part of a wide research project aimed to elucidate the mecha­nism of the metabolic activation of the antitumor imidazoacridinone agent C-1311 se­lected for clinical trials. The objectives of the investigations presented here were: (i) to examine the enzymatic transformation of the reference compound 2-hydroxy- acridinone and (ii) to test the similarity between enzymatic and electrochemical oxida­tion of acridinone compounds. This similarity was searched with respect to the useful­ness of the electrochemical results for further studies on the metabolic oxidation of imidazoacridinone antitumor drugs. The enzymatic oxidation of 2-hydroxyacridinone was performed with a model system containing various amounts of horseradish peroxidase and hydrogen peroxide and was followed by UV-VIS spectroscopy and by HPLC. One product of the reaction was isolated and its chemical structure was identi­fied. It was shown that 2-hydroxyacridinone was transformed by the studied system in a manner dependent on the amount of the enzyme and on the compound/H2O2 ratio. While under mild reaction conditions the transformation ran slowly to yield only one product, p1, independently of the reaction time, higher enzyme concentration re­sulted in several steps of transformation. Product p1 turned out to be a dimer: 1,1-bi(2-hydroxyacridinone). A comparison of the results of the enzymatic transfor­mations of 2-hydroxyacridinone presented here with studies on the electrochemical oxidation reported earlier allowed us to show both transformations to be similar as far as the reaction pathway and two reaction products are concerned.

Słowa kluczowe

EN

enzymatic transformation; antitumour acridinone; enzyme activity; antitumour imidazoacridinone; 2-hydroxyacridinone; peroxidase-mediated oxidation; electrochemical transformation; imidazoacridinone agent

• Wydawca: -
• Czasopismo: Acta Biochimica Polonica
• Rocznik: 2003
• Tom: 50
• Numer: 2
• Opis fizyczny: p.515-525,fig.

Twórcy

autor

Mazerska Z.

• Gdansk University of Technology, G.Narutowicza 11-12, 80-952 Gdansk, Poland

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