A novel series of sanguinarine (SA) derivatives were synthesized and evaluated as anti-non-small cell lung cancer (NSCLC) agents. The compounds inhibited A549 and H1975 NSCLC cells with IC50 values of 0.96 - >30 μM and 0.79 - >30 μM, respectively. Compounds 8d-8j exhibited low micromolar inhibitory activity and indicated that the C6-position of SA was tolerated to be substituted by hydrophilic groups and CN. Further investigation of their mechanism of action showed that compound 8h induced apoptosis of A549 and H1975 cells by inhibiting the Akt signaling pathway and elevating the reactive oxygen species (ROS). This study provided a strategy for developing new anti-cancer agents.
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