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

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

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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

Keywords

  • indolo[2,3-a]carbazole
  • N-riboside
  • dipeptide
  • synthesis
  • cytotoxic activity