The ability of new formamidine sugar-modified derivatives of daunorubicin to stimulate free radical formation in three enzymatic systems: NADH dehydrogenase, NADPH cytochrome p450 reductase and xanthine oxidase

• Autorzy: Pawlowska J. , Tarasiuk J. , Borowski E. , Wasowska M. , Oszczapowicz I. , Wolf C.R.
• Języki publikacji: EN

Abstrakty

EN

Some sterically hindered N-substituted derivatives of daunorubicin are known to be poor substrates for NADH dehydrogenase, NADPH cytochrome P450 reductase and xanthine oxidase. In consequence, poor oxygen radical generation by these compounds is observed. In this study we examined a new family of sugar-N-substituted derivatives of daunorubicin bearing a bulky substituent introduced on the nitrogen atom through the amidine spacer. These compounds were found to be very active in radical formation catalyzed by all three studied enzymes. Thus, the introduction of a heterocyclic ring, even if it is bulky but flexible, on the nitrogen atom of daunosamine moiety through the one-atom spacer (amidine group), does not induce the steric hindrance effect on the interaction of daunorubicin derivatives with these flavoprotein enzymes.

Słowa kluczowe

EN

xanthine oxidase; sugar-N-substituted derivative; antitumour drug; daunorubicin; formamidine derivative; adriamycin; dehydrogenase; human cancer; enzyme system; free radical; flavoprotein enzyme; cytochrome P450; reductase

• Wydawca: -
• Czasopismo: Acta Biochimica Polonica
• Rocznik: 2000
• Tom: 47
• Numer: 1
• Opis fizyczny: p.141-147,fig.

Twórcy

autor

Pawlowska J.

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

autor

Tarasiuk J.

autor

Borowski E.

autor

Wasowska M.

autor

Oszczapowicz I.

autor

Wolf C.R.

Bibliografia

• 1. Abdella, B.R.J. & Fisher, J. (1985) A chemical perspective on the anthracycline antitumor antibiotics. Environ. Health Perspect. 64, 3-18.
• 2. Lown, J.W. (1993) Discovery and development of anthracycline antitumor antibiotics. Chem. Soc. Rev. 165-176.
• 3. Olson, R.D. & Mushlin, P.S. (1990) Doxorubicin cardiotoxicity: Analysis of prevailing hypothesis. J. FASEB4, 3076-3086.
• 4. Havlin, K.A. (1992) Cardiotoxicity of anthracyclines and other antineoplastic agents. Cardiovascular Toxicology; 2nd edn. (Acosta, D., ed.) pp. 143-164, Raven Press Ltd., New York.
• 5. Davies, K.J.A. & Doroshow, J.H. (1986) Redox cycling of anthracyclines by cardiac mitochondria. I. Anthracycline radical formation by NADH dehydrogenase. J. Biol. Chem. 261, 3060-3067.
• 6. Kharasch, E.D. & Novak, R.F. (1983) Bis (alkylamino) anthracenedione antineoplastic agent metabolic activation by NADPH-cytochrome P-450 reductase and NADH dehydrogenase: Diminished activity relative to anthracyclines. Arch. Biochem. Biophys. 224, 682-694.
• 7. Pan, S.S. & Bachur, N.R. (1980) Xanthine oxidase catalysed reductive cleavage of anthracycline antibiotics and free radical formation. Mol. Pharmacol. 17, 95-99.
• 8. Doroshow, J.H. (1983) Effect of anthracycline antibiotics on oxygen radical formation in rat heart. Cancer Res. 43, 460-472.
• 9. Powis, G. (1989) Free radical formation by antitumour quinones. Free Radical Biol. Med. 6, 63-101.
• 10. Tarasiuk, J., Garnier-Suillerot, A., Stefanska, B. & Borowski, E. (1992) The essential role of anthraquinones as substrates for NADH dehydrogenase in their redox cycling activity. Anti-Cancer Drug Design 7, 329-340.
• 11. Tarasiuk, J., Stefanska, B. & Borowski, E. (1990) Low stimulation of NADH oxidation and oxygen consumption by 5-iminodaunorubicin and its derivatives. Acta Biochim. Polon. 37, 251-259.
• 12. Frank, P. & Novak, R.F. (1986) Effects of anthrapyrazole antineoplastic agents on lipid peroxidation. Biochem. Biophys. Res. Commun. 140, 797-807.
• 13. Tarasiuk, J., Tkaczyk-Gobis, K., Stefanska, B., Dzieduszycka, M., Priebe, W., Martelli, S. & Borowski, E. (1998) The role of structural factors of anthraquinone compounds and their quinone-modified analogues in NADH dehydrogenase catalysed oxygen radical formation. Anti-Cancer Drug Design 13, 923-939.
• 14. Tarasiuk, J., Pawlowska, J., Dzieduszycka, M., Wolf, C.R., Priebe, W. & Borowski, E. (1997) The role of structural factors of antitumor anthraquinones and their analogs in the mediation of one-electron transfer catalysed by xanthine oxidase and NADPH-cytochrome P450-reductase. 6th International Symposium on Molecular Aspects ofChemotherapy, Gdansk 9-12 VII 1997, Abstract Book, 96.
• 15. Stefanska, B., Dzieduszycka, M., Martelli, S., Tarasiuk, J., Bontemps-Gracz, M. & Borowski, E. (1993) 6-[(Aminoalkyl)amino]-substituted 7H-benzo[e]perimidin-7-ones as novel antineoplastic agents. Synthesis and biological evaluation. J. Med. Chem. 36, 38-41.
• 16. Stefanska, B., Borowski, E., Falkowski, L. & Martelli, S. (1986) Synthesis and antileukemic activity of some novel N-substituted derivatives of daunorubicin. Polish J. Chem. 60, 525-529.
• 17. Oszczapowicz, I., Grodner, J., Radzikowski, C., Kusnierczyk, H. & Opolski, A. (1997). Polish patent application - P 322756.
• 18. Tong, G.L., Wu, H.Y., Smith, T.H. & Henry, D.W. (1979) Adriamycin analogues. 3. Synthesis of N-alkylated anthracyclines with enhanced activity and reduced cardiotoxicity. J. Med. Chem. 22, 912-918.
• 19. Yasukochi, Y. & Masters, B.S.S. (1976) Some properties of a detergent solubilized NADPH cytochrome (cytochrome P450) reductase purified by biospecific affinity chromathography. J. Biol. Chem. 251, 5337-5344.
• 20. Wolf, C.R., Lewis, A.D., Carmichael, J., Ansell, J., Adams, D.J., Hickson, I.D., Harris, A., Balkwill, F.R., Griffin, D.B. & Hayes, J.D. (1987) Glutathione S-transferase expression in normal and tumor cells resistant to cytotoxic drugs; in Glutathione S-transferase and Carcinogenesis (Mantle, T.J., Pickett, C.B., Hayes, J. D., eds.) pp. 199-212, Taylor & Francis, London.
• 21. Azzi, A., Montecucco, C. & Richter, C. (1975) The use of acetylated ferricytochrome c for the detection of superoxide radicals produced in biological membranes. Biochem. Biophys. Res. Commun. 65, 597-603.