A series of new berbamine derivatives were synthesized, and their cytotoxic activity was evaluated against Human T-cell lymphoma cell line H9 and multiple myeloma cell line RPMI8226 in vitro. Compared with berbamine, the cytotoxicity of the modified derivatives was enhanced, especially simultaneously substituted at OH and 5-position. Compounds 2a and 4b exhibited high antitumor activity. The IC(50) value of compound 2a was 0.30 muM for RPMI8226 cells, and the IC(50) value of compound 4b was 0.36 muM for H9 cells, whereas berbamine IC(50) values were 4.0 muM for H9 cells and 6.19 muM for RPMI8226 cells, respectively.[Formula: see text].