Targeting mitochondria: Esters of rhodamine B with triterpenoids are mitocanic triggers of apoptosis.

Abstract Triterpenoic acids, ursolic acid ( 1 ), oleanolic acid ( 2 ), glycyrrhetinic acid ( 3 ) and betulinic acid ( 4 ) were converted into their corresponding methyl 5 – 8 and benzyl esters 9 – 12 or benzyl amides 21 – 24 . These derivatives served as starting materials for the synthesis of pink colored rhodamine B derivatives 25 – 36 which were screened for cytotoxicity in colorimetric SRB assays. All of the compounds were cytotoxic for a variety of human tumor cell lines. The activity of the benzyl ester derivatives 29 – 32 was lower than the cytotoxicity of the methyl esters 25 – 28 . The benzyl amides 33 – 36 were the most cytotoxic compounds of this series. The most potential compound was a glycyrrhetinic acid rhodamine B benzyl amide 35 . This compound showed activity against the different cancer cell lines in a two-digit to low three-digit nano-molar range. Staining experiments combined with fluorescence microscopy showed that this compound triggered apoptosis in A2780 ovarian carcinoma cells and acted as a mitocan.