Synthesis and Antitumor Activity of C-3(R) Hydroxy Modified Betulinic Acid Derivatives

Four novel betulinic acid (BA) derivatives modified at the C-3 position were prepared by the Mitsunobu reaction and subsequently evaluated for antitumor activity against four common cancer cell lines in vitro. The results from the MTT assay revealed that the four tested compounds showed remarkable cytotoxic activity against four cancer cell lines, much better than BA. Western blotting results indicated that the four compounds, especially compound 2c , caused a significant up-regulation expression of the caspase-12 in CT26 cell. Our results showed that configuration inversions of chiral C-3 of BA could also produce BA derivatives with potent antitumor activity.