MS, and IR, 1H NMR and 13C NMR spectroscopy were employed to elucidate 4 novel evodiamine (EVO) derivatives with nitro, amino, and methoxy groups, namely 2-NO2-EVO (7a), 10-OCH3-2-NO2-EVO (7b), 2-NH2-EVO (8a), and 10-OCH3-2-NH2-EVO (8b). The amino compounds (8a, 8b) were obtained by the reduction of nitro derivatives (7a, 7b) with SnCl2/HCl. The antiproliferative activities of these compounds were tested by Cell Counting Kit-8 assay for 48 h against the MDA-MB-231 and sw620 cancer cell lines, as well as the normal LO2 cells. The in vitro experiment showed that 8a possesses the most potent inhibitory activities against MDA-MB-231 and SW620 cells, with IC50 values of 0.79 and 1.28 μM, respectively. The cytotoxicity of 8a against the 2 cancer cell lines was higher than that of EVO. © The Author(s) 2022.