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Triphenylphosphonium cations of betulinic acid derivatives: synthesis and antitumor activity

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Abstract

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.

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Acknowledgements

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).

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Authors and Affiliations

  1. Institute of Petrochemistry and Catalysis, Russian Academy of Sciences, 141 Prospekt Oktyabrya, Ufa, 450075, Russian Federation

    Anna Yu. Spivak, Darya A. Nedopekina, Rezeda R. Khalitova, Rinat R. Gubaidullin & Viktor N. Odinokov

  2. Innovative Pharmacology Research (IPHAR), 8/8 Prospekt Akademicheskii, Tomsk, 634055, Russian Federation

    Yuriy P. Bel’skii, Natalia V. Bel’skaya & Veniamin A. Khazanov

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  1. Anna Yu. Spivak
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  2. Darya A. Nedopekina
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  3. Rezeda R. Khalitova
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  8. Veniamin A. Khazanov
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Correspondence to Anna Yu. Spivak.

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Spivak, A.Y., Nedopekina, D.A., Khalitova, R.R. et al. Triphenylphosphonium cations of betulinic acid derivatives: synthesis and antitumor activity. Med Chem Res 26, 518–531 (2017). https://doi.org/10.1007/s00044-016-1771-z

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  • DOI: https://doi.org/10.1007/s00044-016-1771-z

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