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Polymethylene derivatives of nucleic bases with ω-functional groups: VI. [8-(2-oxocyclohexyl)-9-oxooctyl]pyrimidines as potential inhibitors of pyrimidine phosphorylases

Abstract

New polymethylene derivatives of nucleic bases with β-diketo function in ω-position were prepared by alkylation of uracil, thymine, and cytosine. Their physicochemical properties and effect on the E. coli uridine and thimidine phosphorylases were studied.

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Abbreviations

TP:

thymidine phosphorylase from E.coli (EC 2.4.2.4)

UP:

uridine phosphorylase from E. coli (EC 2.4.2.3)

DBU:

1,8-diazabicyclo[5.4.0]undece-7-ene

References

  1. Kritzyn, A.M. and Komissarov, V.V., Bioorg. Khim., 2005, vol. 31, pp. 609–615; Rus. J. Bioorg. Chem., 2005, vol. 31, pp. 549–555.

    Google Scholar 

  2. Makinsky, A.A., Kritzyn, A.M., Ul’yanova, E.A., Zakharova, O.D., and Nevinsky, G.A., Bioorg. Khim., 2000, vol. 26, pp. 735–742; Rus. J. Bioorg. Chem. 2000, vol. 26, pp. 662–668.

    Google Scholar 

  3. Summa, V., Petrocchi, A., Matassa, V.G., Taliani, M., Laufer, R., De Francesco, R., Altamura, S., and Pace, P., J. Med. Chem., 2004, vol. 47, pp. 5336–5339.

    CAS  Article  PubMed  Google Scholar 

  4. Biswal, B.K., Cherney, M.M., Wang, M., Chan, L., Yannopoulos, C.G., Bilimoria, D., Nicolas, O., Bedard, J., and James, M.N.G., J. Biol. Chem., 2005, vol. 280, pp. 18202–18210.

    CAS  Article  PubMed  Google Scholar 

  5. Summa, V., Petrocchi, A., Pace, P., Matassa, V.G., De Francesco, R., Altamura, S., Tomei, L., Koch, U., and Neuner, P., J. Med. Chem., 2004, vol. 47, pp. 14–17.

    CAS  Article  PubMed  Google Scholar 

  6. Wai, J.S., Egbertson, M.S., Payne, L.S., Fisher, T.E., Embrey, M.W., Tran, L.O., Melamed, J.Y., et al., J. Med. Chem., 2000, vol. 43, pp. 4923–4926.

    CAS  Article  PubMed  Google Scholar 

  7. Grobler, J.A., Stillmock, K., Hu, B., Witmer, M., Felock, P., Espeseth, A.S., Wolfe, A., Egbertson, M., Bourgeois, M., Melamed, J., Wai, J.S., Young, S., Vacca, J., and Hazuda, D.J., Proc. Natl. Acad. Sci. USA, 2002, vol. 99, pp. 6661–6666.

    CAS  Article  PubMed  Google Scholar 

  8. Long, Y.-Q., Jiang, X.-H., Dayam, R., Sanchez, T., Shoemaker, R., Sei, S., and Neamati, N., J. Med. Chem., 2004, vol. 47, pp. 2561–2573.

    CAS  Article  PubMed  Google Scholar 

  9. Kel’vin, A.V., Current Organic Chemistry, 2003, vol. 7, pp. 1691–1711.

    Article  Google Scholar 

  10. Kritzyn, A.M. and Komissarov, V.V., Bioorg. Khim., 2004, vol. 30, pp. 487–492; Rus. J. Bioorg. Chem., 2004, vol. 30, pp. 436–440.

    Google Scholar 

  11. Kritzyn, A.M., Vesalainen, J., and Komissarov, V.V., Bioorg. Khim., 2005, vol. 31, pp. 288–294; Rus. J. Bioorg. Chem. 2005, vol. 31, pp. 256–262.

    Google Scholar 

  12. Esteban-Gamboa, A., Balzarini, J., Esnouf, R., De Clercq, E., Camarasa, M.-J., and Perez-Perez, M.-J., J. Med. Chem., 2000, vol. 43, pp. 971–983.

    CAS  Article  PubMed  Google Scholar 

  13. Konstantinova, I.D., Leont’eva, N.A., Galegov, G.A., Ryzhova, O.I., Chuvikovsky, D.V., Antonov, K.V., Esipov, R.S., Taran, S.A., Verevkina, K.N., Feofanov, S.A., and Miroshnikov, A.I., Bioorg. Khim., 2004, vol. 30, pp. 613–620; Rus. J. Bioorg. Chem., 2004, vol. 30, pp. 553–560.

    CAS  PubMed  Google Scholar 

  14. Moghaddam, A., Zhang, H.T., Fan, T.P.D., Hu, D.E., Lees, V., Turley, H., Fox, S.B., Gatter, K.C., Harris, A.L., and Bicknell, R., Proc. Natl. Acad. Sci. USA, 1995, vol. 92, pp. 998–1002.

    CAS  Article  PubMed  Google Scholar 

  15. Matsushita, S., Nitanda, T., Furukawa, T., Sumizawa, T., Tani, A., Nishimoto, K., Akiba, S., Miyadera, K., Fukushima, M., Yamada, Y., Yoshiba, H., Kanzaki, T., and Akiyama, S., Cancer Res., 1999, vol. 59, pp. 1911–1916.

    CAS  PubMed  Google Scholar 

  16. Bookser, B.C., Kasibhatla, S.R., Appleman, J.R., and Erion, M.D., J. Med. Chem., 2000, vol. 43, pp. 1495–1507.

    CAS  Article  PubMed  Google Scholar 

  17. Friess, S.L., J. Am. Chem. Soc., 1949, vol. 71, pp. 2571–2575.

    CAS  Article  Google Scholar 

  18. Hünig, S., Lücke, E., and Benzing, E., Chem. Ber., 1958, vol. 91, pp. 129–133.

    Article  Google Scholar 

  19. Stork, G., Brizzolara, A., Landesman, H., Szmuszkovicz, J., and Terrell, R., J. Amer. Chem. Soc, 1963, vol. 85, pp. 207–222.

    CAS  Article  Google Scholar 

  20. Jones, R.A. and Stokes, M.J., Tetrahedron, 1984, vol. 40, pp. 1051–1060.

    CAS  Article  Google Scholar 

  21. Panova, N.G., Alekseev, K.S., Kuz’michev, A.S., Shcheveleva, E.V., Gavryushov, S.A., Polyakov, K.M., Kritsyn, A.M., Mikhailov, S.N., Esipov, R.S., and Miroshnikov, A.I., Biokhimiya (Moscow), 2007, vol. 72, pp. 27–35.

    Google Scholar 

  22. Panova, N.G., Shcheveleva, E.V., Alekseev, K.S., Mukhorotov, V.G., Zuev, A.N., Mikhailov, S.N., Esipov, R.S., Chuvikovskii, D.V., and Miroshnikov, A.I., Mol. Biol. (Moscow), 2005, vol. 38, pp. 907–913.

    Google Scholar 

  23. Tietze, L. and Eicher, T., Reaktionen und Synthesen im organische-chemischen Praktikum und Forschungslaboratorium, New York: Georg Thieme Verlag Stuttgart, 1991. Translated under the title Preparativnaya organicheskaya khimiya, Moscow: Mir, 1999.

    Book  Google Scholar 

  24. Degering, E.F. and Boatright, L.G., J. Am. Chem. Soc., 1950, vol. 72, pp. 5137–5139.

    CAS  Article  Google Scholar 

  25. Esipov, R.S., Gurevich, A.I., Chuvikovsky, D.V., Chupova, L.A., Muravyova, T.I., and Miroshnikov, A.I., Protein Expr. Purif., 2002, vol. 24, pp. 56–60.

    CAS  Article  PubMed  Google Scholar 

  26. Krenitsky, T.A., Koszalka, G.W., and Tuttle, J.V., Biochemistry, 1981, vol. 20, pp. 3615–3621.

    CAS  Article  PubMed  Google Scholar 

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Correspondence to A. M. Kritzyn.

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Original Russian Text © V.V. Komissarov, N.G. Panova, A.M. Kritzyn, 2008, published in Bioorganicheskaya Khimiya, 2008, Vol. 34, No. 1, pp. 75–82.

For communication V, see [1].

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Komissarov, V.V., Panova, N.G. & Kritzyn, A.M. Polymethylene derivatives of nucleic bases with ω-functional groups: VI. [8-(2-oxocyclohexyl)-9-oxooctyl]pyrimidines as potential inhibitors of pyrimidine phosphorylases. Russ J Bioorg Chem 34, 67–73 (2008). https://doi.org/10.1134/S1068162008010093

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  • DOI: https://doi.org/10.1134/S1068162008010093

Key words

  • alkylation
  • β-diketones
  • nucleosides
  • polymethylene analogues
  • pyrimidine phosphorylases