Synthesis and in vitro antitumor evaluation of betulin acid ester derivatives as novel apoptosis inducers

Nineteen betulin derivatives modified at the C-3 and C-28 positions were synthesized and assessed for antitumor activities against the MGC-803, PD, Bcap-37, A375, and MCF-7 human cancer cell lines in vitro by MU assay. Some derivatives (compounds 3a-3d and 5) displayed strong antitumor properties, with IC50 values between 4 and 18 mu M. Compound 3c, containing piperidine group at C-28 position, had IC50 values of 4.3, 4.5, 5.2, 7.5, and 5.2 mu M on the five cancer cell lines, respectively. Subsequent fluorescence staining and flow cytometric analysis indicated that compound 3c induced apoptosis in MGC-803 cell line, with an apoptosis ratio of 31.11% after 36 h of treatment at 10 mu M 3c. (C) 2015 Elsevier Masson SAS. All rights reserved.