Similarity between enzymatic and electrochemical oxidation of 2-hydroxyacridinone, the reference compound of antitumor imidazoacridinones.
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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.
- Acheson RM. (1973) Acridines. In The chemistry of heterocyclic compounds.Acheson RM. ed, p 141. John Willey & Sons.
- Cakala M, Mazerska Z, Donten M, Stojek Z. (1999) Electroanalytical and acid-base properties of imidazoacridinone. Anal Chim Acta.; 379: 209.
- Chen TR, Dryhurst G. (1982) Peroxidase- catalysed oxidation of 7,9-dimethyluric acid. Electrochemical insights. Bioelectrochem Bioenerg.; 11: 75-88.
- Cholody WM, Martelli S, Lukowicz J, Konopa J. (1990a) 5-[(Aminoalkyl)amino]-imidazo- (4,5,1-de)acridin-6-ones as a novel class of antineoplastic agents. Synthesis and biological activity. J Med Chem.; 33: 49-52.
- Cholody WM, Martelli S, Konopa J. (1990b) 8-Substituted 5-[(aminoalkyl)amino]- 6H-v-triazolo(4,5,1-de)acridin-6-ones as potential antineoplastic agents. Synthesis and biological activity. J Med Chem.; 33: 2852-6.
- Cholody WM, Martelli S, Konopa J. (1992) Chromophore-modified antineoplastic imidazoacridinones. Synthesis and activity against murine leukemias. J Med Chem.; 35: 378-82.
- Cholody WM, Horowska B, Martelli S, Konopa J. (1996) Structure-activity relationship for antineoplastic imidazoacridinones: Synthesis and antileukemic activity in vivo. J Med Chem.; 39: 1028-32.
- Dryhurst G. (1985) Insights provided by electrochemical techniques into the biological redox chemistry of purines. Bioelectrochem Bioenerg.; 14: 251-74.
- Dziegielewski J, Konopa J. (1996) Interstrand crosslinking of DNA in tumor cells by a new group of antitumor imidazoacridinones. Proc Am Assoc Cancer Res.; 37: Abst.2800.
- Dziegielewski J, Konopa J, (1998) Characterisation of covalent binding to DNA of antitumor imidazoacridinone C-1311, after metabolic activation. Ann Oncol.; 9 (Supl. 1): 137.
- Favretto D, Bertazzo A, Costa CVL, Allegri G, Donato N, Traldi P. (1998) The role of peroxidase in the oligomerization of 5-hydroxytryptamine investigated by matrix-assisted laser desorption/ionisation mass spectrometry. Rapid Commun Mass Spectrom.; 12: 193-7.
- Fujitake N, Suzuki T, Fukumoto M, Oji Y. (1998) Predomination of dimers over naturally occurring anthraquinones in soil. J Nat Prod.; 61: 189-92.
- Goyal RN. (1994) Oxidation chemistry and biochemistry of some biologically important purines and indoleamines. Bioelectrochem Bioenerg.; 33: 75-81.
- Hapiot P, Neudeck A, Pinson J, Fulcrand H, Neta P, Rolando C. (1996) Oxidation of caffeic acid and related hydroxycinnamic acids. J Electroanal Chem.; 405: 169-76.
- Hu T, Dryhurst G. (1997) Electrochemical and peroxidase O2-mediated oxidation of indole-3-acetic acid at physiological pH. J Electroanal Chem.; 432: 7-18.
- Massini J, Aragon S, Nyasulu F. (1997) Electrochemistry of brucine. 2. The brucine-based determination of nitrate. Anal Chem.; 69: 1077-81.
- Mazerska Z, Zamponi S, Marassi R, Martelli S, Konopa J. (1997) Electrochemical oxidation of antitumor imidazoacridinone derivatives and the reference 2-hydroxyacridinone. J Electroanal Chem.; 427: 71-8.
- Mazerska Z, Augustin E, Skladanowski A, Bibby MC, Double JA, Konopa J. (1998a) C-1311 NSC-645809. Drugs Fut.; 23: 702-6.
- Mazerska Z, Gorlewska K, Kraciuk A, Konopa J. (1998b) The relevance of enzymatic oxidation by horseradish peroxidase to antitumour potency of imidazoacridinone derivatives. Chem-Biol Interact.; 115: 1-22.
- Mazerska Z, Dziegielewski J, Konopa J. (2001) Enzymatic activation of a new antitumor drug, 5-diethylamino-8-hydroxyimidazoacridinone, C-1311, observed after its intercalation into DNA. Biochem Pharmacol.; 61: 685-94.
- Mazerska Z, Zamponi S, Marassi R, Sowinski P, Konopa J. (2002) The products of electro- and photochemical oxidation of 2-hydroxyacridinone, the reference compound of antitumor imidazoacridinone drivatives. J Electroanal Chem.; 521: 144-54.
- Michon T, Chenu M, Kellershon N, Desmadril M, Gueguen J. (1997) Horseradish peroxidase oxidation of tyrosine-containing peptides and their subsequent polymerisation: a kinetic study. Biochemistry.; 36: 8504-13.
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