Medicinal Chemistry Research

, Volume 26, Issue 3, pp 518–531 | Cite as

Triphenylphosphonium cations of betulinic acid derivatives: synthesis and antitumor activity

  • Anna Yu. Spivak
  • Darya A. Nedopekina
  • Rezeda R. Khalitova
  • Rinat R. Gubaidullin
  • Viktor N. Odinokov
  • Yuriy P. Bel’skii
  • Natalia V. Bel’skaya
  • Veniamin A. Khazanov
Original Research


A series of lupane triterpenoid conjugates with the triphenylphosphonium cation, in which the terpenoid molecules are linked to one or two triphenylphosphonium moieties at the С-2, С-28, or С-30 positions by carbon–carbon or ester bonds, have been designed and synthesized as potential anti-cancer agents. The pharmacological results showed that all of the prepared triphenylphosphonium salts displayed considerable antitumor activities against the tested cancer murine tumor (Ehrlich ascites carcinoma, (Р-815), and human tumor (MCF-7) (IC50 < 2 μg/mL)) cell lines. The presence of the triphenylphosphonium cation in the triterpenoid conjugates markedly enhanced the cytotoxic action as compared to the parent compound (betulinic acid) (IC50 24.7 μg/mL for Ehrlich cells and 18.7 μg/mL for Р-815 cells), while the correlation between the cytotoxic activity and the chemical structure of phosphonium salts was not observed.


Pentacyclic triterpenoids Betulin Betulinic acid Triphenylphosphonium derivatives Anticancer agents 



The authors are deeply thankful to the staff members of the analytical center “Agidel” at Institute of Petrochemistry and Catalysis of RAS for spectral measurement. This work was performed under financial support from the Russian Science Foundation (Grant 16-13-10051).

Compliance with ethical standards

Conflict of interest

The authors declare no Conflict of interest.

Supplementary material

44_2016_1771_MOESM1_ESM.doc (14.4 mb)
Supplementary Material


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Copyright information

© Springer Science+Business Media New York 2016

Authors and Affiliations

  • Anna Yu. Spivak
    • 1
  • Darya A. Nedopekina
    • 1
  • Rezeda R. Khalitova
    • 1
  • Rinat R. Gubaidullin
    • 1
  • Viktor N. Odinokov
    • 1
  • Yuriy P. Bel’skii
    • 2
  • Natalia V. Bel’skaya
    • 2
  • Veniamin A. Khazanov
    • 2
  1. 1.Institute of Petrochemistry and Catalysis, Russian Academy of SciencesUfaRussian Federation
  2. 2.Innovative Pharmacology Research (IPHAR)TomskRussian Federation

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