2,9-Dimethoxymethylboldine (2), 2,9-dimethoxymethyl-3-bromoboldine (3) and 2,9-dimethoxymethyl-3-diphenylphosphinylboldine (4) have been synthesized in an effort to find compounds with potential pharmacological applications. The cytotoxic activities of the natural precursor 1 and these three derivatives have been measured as IC₅₀ inhibitory growth. The diphenylphosphinyl derivative 4 showed a significant cytotoxic activity on two breast cancer cell lines, namely MCF-7 and MDA-MB-231, with IC₅₀ values of 55.5 and 62.7 [µM], respectively. These results suggest that the kind of structural modifications introduced to synthesize compound 4 represent a promising way to enhance the cytotoxic activity of boldine derivatives.