Synthesis and Antitumor Activity of 17-carboxylic acid M odified A mide D erivatives of 3-hydroxy betulinic acid

 A novel series of 17-carboxylic acid modified amide derivatives of 3-hydroxy betulinic acid (1) were prepared and tested in vitro against five cell lines: A549 (human lung carcinoma), BEL-7402 (human hepatoma), SF-763 (human cerebroma), B16 (mice melanoma) and HL-60 (human leukaemia) . Within this series of compounds, 4a (IC 50=21.08 μ M in SF-763, IC 50=21.63 μ M in HL-60), 4b (IC 50=28.45 μ M in HL-60,IC 50=29.32 μ M in BEL-7402 ) and 6g (IC 50=26.09 μM in BEL-7402, IC 50=22.65 μM in HL-60) have the mo re potent cytotoxic activity than lead compound 1. The preliminary structure-activity relationship analysis of the C-28 amide derivatives is also discussed.