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2003 | 50 | 2 | 515-525
Article title

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

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EN
Abstracts
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-hydroxyacridinone 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.
Publisher

Year
Volume
50
Issue
2
Pages
515-525
Physical description
Dates
published
2003
received
2003-02-06
revised
2003-03-13
accepted
2003-03-20
Contributors
  • Department of Pharmaceutical Technology and Biochemistry, Chemical Faculty, Gdańsk University of Technology, Gdańsk, Poland
References
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Document Type
Publication order reference
Identifiers
YADDA identifier
bwmeta1.element.bwnjournal-article-abpv50i2p515kz
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