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Synthesis of a new betulinic acid glycoconjugate with N-acetyl-d-galactosamine for the targeted delivery to hepatocellular carcinoma cells

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Russian Chemical Bulletin Aims and scope

Abstract

A new promising conjugate of betulinic acid with N-acetyl-d-galactosamine was synthesized by the simple reaction sequence: esterification and copper-catalyzed azide-alkyne cycloaddition. The obtained glycoderivative exhibited high activity against hepatocarcinoma cell lines in vitro, selectivity of cytotoxic action, and excellent binding to the asialoglycoprotein receptor (ASGPR) of hepatocytes. Its affinity to the ASGPR was established by surface plasmon resonance spectroscopy and confirmed by molecular docking in silico. An original approach was proposed to enhance the cytotoxic properties of C-28 betulinic esters by introducing a hemioxalate fragment bearing free carboxyl group into the C(3) position of ring A.

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Authors and Affiliations

  1. Department of Chemistry, Lomonosov Moscow State University, 1 Leninskie Gory, 119991, Moscow, Russian Federation

    A. S. Olshanova, E. Yu. Yamansarov, E. I. Seleznev, S. V. Kovalev, A. V. Lopuhov, D. A. Skvortsov, S. A. Evteev, N. L. Klyachko, E. K. Beloglazkina & A. G. Majouga

  2. Skolkovo Institute of Science and Technology, 100 ul. Novaya, 143025, Skolkovo, Russian Federation

    N. L. Klyachko

  3. Institute of Biochemistry and Genetics, Ufa Scientific Center of the Russian Academy of Sciences, 71 prosp. Oktyabrya, 450054, Ufa, Russian Federation

    Ya. A. Ivanenkov

  4. Moscow Institute of Physics and Technology (State University), 9 Institutskiiper., 141701, Dolgoprudnyi, Moscow region, Russian Federation

    Ya. A. Ivanenkov

  5. National University of Science and Technology MISiS, 4 Leninskiiprosp., 119049, Moscow, Russian Federation

    A. G. Majouga

  6. Dmitry Mendeleev University of Chemical Technology of Russia, 1 Build., 9 Miusskaya pl., 125047, Moscow, Russian Federation

    A. G. Majouga

Authors
  1. A. S. Olshanova
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  2. E. Yu. Yamansarov
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  3. E. I. Seleznev
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  4. S. V. Kovalev
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  5. A. V. Lopuhov
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  6. D. A. Skvortsov
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  7. S. A. Evteev
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  8. N. L. Klyachko
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  9. E. K. Beloglazkina
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  10. Ya. A. Ivanenkov
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  11. A. G. Majouga
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Corresponding author

Correspondence to E. Yu. Yamansarov.

Additional information

Dedicated to Academician of the Russian Academy of Sciences V. V. Lunin on the occasion of his 80th birthday.

Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 1, pp. 0158–0163, January, 2020.

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Olshanova, A.S., Yamansarov, E.Y., Seleznev, E.I. et al. Synthesis of a new betulinic acid glycoconjugate with N-acetyl-d-galactosamine for the targeted delivery to hepatocellular carcinoma cells. Russ Chem Bull 69, 158–163 (2020). https://doi.org/10.1007/s11172-020-2737-3

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  • DOI: https://doi.org/10.1007/s11172-020-2737-3

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