Background: Berberine (BBR), an isoquinoline plant alkaloid isolated from plants such as Coptis
chinensis and Hydrastis canadensis, own multiple pharmacological activities.
Objective: In this study, seven BBR derivatives were synthesized and their anticancer activity against HeLa
cervical and A549 human lung cancer cell lines were evaluated in vitro.
Methods: The anti-cancer activity was measured by MTT assay, and apoptosis was demonstrated by the annexin
V-FITC/PI staining assay. The intracellular oxidative stress was investigated through DCFH-DA assay. The
molecular docking study was carried out in molecular operating environment (MOE).
Results: Compound B3 and B5 showed enhanced anti-cancer activity compared with BBR, the IC50 for compound
B3 and B5 were significantly lower than BBR, and compound B3 at the concentration of 64 or 128 µM
induced apoptosis in HeLa and A549 cell lines. The reactive oxygen species (ROS) was generated in both cell
lines when treated with 100 µM of all the compounds, and compound B3 and B5 induced higher activity in the
generation of ROS, while compound B3 exhibited the highest activity, these results are in accordance with the
cytotoxicity results, indicating the cytotoxicity were mostly generated from the oxidative stress. In addition,
molecular docking analysis showed that compound B3 had the greatest affinity with Hsp90. Upon binding, the
protective function of Hsp90 was lost, which might explain its higher cytotoxicity from molecular interaction
Conclusion: All the results demonstrated that compound B3 and B5 showed significantly higher anti-cancer
ability than BBR, and compound B3 is a promising anticancer drug candidate.