Triphenylphosphonium cations of betulinic acid derivatives: synthesis and antitumor activity

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 D-2, D-28, or D-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, (D -815), and human tumor (MCF-7) (IC50 < 2 mu g/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 mu g/mL for Ehrlich cells and 18.7 mu g/mL for D -815 cells), while the correlation between the cytotoxic activity and the chemical structure of phosphonium salts was not observed.