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N6-dipeptide derivatives of N12-ribosyl-indolo[2,3-a]carbazole

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Abstract

N6-derivatives of N12-indolo[2,3-a]pirrolo[3,4-c]carbazole-5,7-dione are synthesized as potential antitumor agents. The pyrrol N6 atom of these compounds is included into the dipeptide residue of the general formula >N6-(CH2) n -CO-Ala/βAla-OMe (n = 2 or 3). These compounds are synthesized by the reaction in DMF at 130°C between 13-methyl-12-(2,3,4-tri-O-acetyl-β-D-ribopyranosyl)indolo[2,3-a]furano[3,4-c]carbazole-5,7-dione and dipeptides containing the free N-terminal amino group. The nitrogen atom of the peptide amino group replaces O6 in the furan ring and is embedded as the N6 imide nitrogen atom of pyrrol. The ability of the compounds obtained to inhibit the growth of the SKOV3 human ovarian carcinoma cells was studied. The only derivative containing the >N6-(CH2)3-CO-L-Ala-OMe radical showed the cytotoxic activity with an inhibitory concentration of IC50 = 8 μM.

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Abbreviations

GABA:

γ-aminobutyric acid

IC:

inhibition concentration

TEA:

triethylamine

IPC:

indolo[2,3-a]pyrrolo[3,4-c]carbazole-5,7-dione

References

  1. Knölker, H.-J. and Reddy, K.R., Chem. Rev., 2002, vol. 102, pp. 4303–4427.

    Article  PubMed  Google Scholar 

  2. Sánchez, C., Méndez, C., and Salas, J.A., Nat. Prod. Rep., vol. 23, pp. 1007–1045.

  3. Schwandt, A., Mekhail, T., Halmos, B., O’Brien, T., Ma, P.C., Pingfu, F., Ivy, P., and Dowlati, A., J. Thorac. Oncol, 2012, vol. 7, pp. 751–754.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  4. Saif, M.W., Sellers, S., Diasio, R.B., and Douillard, J.-Yv., Anticancer Drugs, 2010, vol. 27, pp. 716–723.

    Google Scholar 

  5. Zembower, D.E., Xie, Y., Koohang, A., Kuffel, M.J., Ames, M.M., Zhou, Y., Mishra, R., Mar, A.A., Flavin, M.T., and Xu, Z.Q., Anticancer Agents Med. Chem, 2012, vol. 12, pp. 1117–1131.

    Article  CAS  PubMed  Google Scholar 

  6. Fu, P., Yang, C., Wang, Y., Liu, P., Ma, Y., Xu, L., Su, M., Hong, K., and Zhu, W., Org. Lett., 2012, vol. 14, pp. 2422–2425.

    Article  CAS  PubMed  Google Scholar 

  7. Animati, F., Berettoni, M., Bigioni, M., Binaschi, M., Cipollone, A., Irrissuto, C., Nardelli, F., and Olivieri, L., Bioorg. Med. Chem. Lett., 2012, vol. 22, pp. 5013–5017.

    Article  CAS  PubMed  Google Scholar 

  8. Pindur, U., Kim, Y.-Sh., and Mehrabani, F., Curr. Med. Chem, 1999, vol. 6, pp. 29–69.

    CAS  PubMed  Google Scholar 

  9. Prudhomme, M., J. Med. Chem., 2003, vol. 38, pp. 123–140.

    Article  CAS  Google Scholar 

  10. Devis, P.D., Hill, C.H., Lawton, G., Nixon, J., Wilkinson, S., Hurst, S., Keech, E., and Turner, S., J. Med. Chem., 1992, vol. 35, pp. 177–184.

    Article  Google Scholar 

  11. Bailly, C., Riou, J.F., Colson, P., Houssier, C., Rodrigues-Pereira, E., and Prudhomme, M., Biochemistry, 1997, vol. 36, pp. 3917–3929.

    Article  CAS  PubMed  Google Scholar 

  12. Prudhomme, M., Curr. Med. Chem. Anticancer Agents, 2004, vol. 4, pp. 435–438.

    Article  CAS  PubMed  Google Scholar 

  13. Mel’nik, S.Ya., Eksperimental’naya onkologiya na rubezhe vekov, Davydov, M.I., Baryshnikov, A.Yu., Ed., Moscow: izdatel’skaya gruppa RONTs im. N.N. Blokhina RAMN, 2003, pp. 281–293.

  14. Trostmann, U., Hartenstein, J., Barth, H., Reck, R., Schächtele, C., Rudolph, K., and Kölch, W., Patent Germanii Ger. Offen DE 42 43 321 A1, 1994

    Google Scholar 

  15. Trostmann, U., Schaechtele, C., Hartenstein, J., Rudolph, K., Barth, H., Reck, R., and Kolch, W., US Patent No. 5750555, 1998.

  16. Smirnova, L.I., Goryunova, O.V., Ektova, L.V., Miniker, T.D., Plikhtyak, I.L., Ustinkina, S.V., and Vlasenkova, N.K., Peptides, 2004. Proceedings of the 3rd International and 28th European Peptide Symposium, Flegel, M., Fridkin, M., Gilon, C., Slaninova, J., Eds. Kenes International, 2005, pp. 603–604.

  17. Bakhmedova, A.A., Garaeva, L.D., Goryunova, O.V., Miniker, T.D., Plikhtyak, I.L., Ektova, L.V., Adanin, V.M., Ivanova, T.P., Yartseva, I.V., and Mel’nik, S.Ya., Bioorg. Khim., 1997, vol. 23, pp. 667–674.

    CAS  Google Scholar 

  18. Nikiforova, N.V. and Radina, L.B., Zh. Org. Khim., 1979, vol. 49, pp. 1878–1883.

    CAS  Google Scholar 

  19. Gronka, Z. and Lammek, B., Synthes, no. is. 1974, pp. 661–662.

    Google Scholar 

  20. Guttman, S. and Boissonnas, R.A., Helv. Chim. Acta, 1958, vol. 41, pp. 1852–1867.

    Article  Google Scholar 

  21. Halpern, B. and Nitecki, D.E., Tetrahedron Lett., 1967, pp. 3031–3033.

    Google Scholar 

  22. ACD/C+H NMR Predictors and DB, Advanced Chemistry Development, Inc., Toronto, On, Canada, www.acdlabs.com, 2012.

  23. Campling B.J., Pym, J., Baker, H.M., Cole, S.P., and Lam, Y.M., Br. J. Cancer, 1991, vol. 63, pp. 75–83.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  24. Zhukova, O.S., Gerasimova, G.N., Shubina, I.Zh., and Kiselevskii, M.V., Byul. Eksper. Biol. Med, 2007, vol. 8, pp. 198–201.

    Google Scholar 

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Authors and Affiliations

  1. Blokhin Russian Cancer Research Center, Russian Academy of Medical Sciences, Kashirskoe sh. 24, Moscow, 115478, Russia

    O. V. Goryunova, G. M. Zakharchuk, O. S. Zhukova & L. V. Fetisova

  2. Scientific Center for Medical Application Products, Ministry of Health of the Russian Federation, Moscow, 127051, Russia

    N. E. Kuzmina

Authors
  1. O. V. Goryunova
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  2. G. M. Zakharchuk
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  3. O. S. Zhukova
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  4. L. V. Fetisova
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  5. N. E. Kuzmina
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Correspondence to O. V. Goryunova.

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Original Russian Text © O.V. Goryunova, G.M. Zakharchuk, O.S. Zhukova, L.V. Fetisova, N.E. Kuzmina, 2014, published in Bioorganicheskaya Khimiya, 2014, Vol. 40, No. 1, pp. 12–19.

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Goryunova, O.V., Zakharchuk, G.M., Zhukova, O.S. et al. N6-dipeptide derivatives of N12-ribosyl-indolo[2,3-a]carbazole. Russ J Bioorg Chem 40, 9–15 (2014). https://doi.org/10.1134/S106816201401004X

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  • DOI: https://doi.org/10.1134/S106816201401004X

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