Triphenylphosphonium cations of betulinic acid derivatives: synthesis and antitumor activity

• DOI: 10.1007/s00044-016-1771-z
• Publication Date: 2017-01-05T05:08:13Z
• Authors: 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
• Keywords: Betulinic acid; Phosphonium; Ehrlich ascites carcinoma; Conjugate; Betulin; IC50

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.