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.

中文翻译：

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血根碱衍生物抗非小细胞肺癌药物的合成及生物学评价

合成了一系列新的血根碱 (SA) 衍生物并作为抗非小细胞肺癌 (NSCLC) 药物进行了评估。这些化合物抑制 A549 和 H1975 NSCLC 细胞，IC ₅₀值分别为 0.96 – >30 μM 和 0.79 – >30 μM。化合物8d-8j表现出低微摩尔抑制活性，表明 SA 的 C6 位可以被亲水基团和 CN 取代。对其作用机制的进一步研究表明，化合物8h通过抑制 Akt 信号通路和提高活性氧 (ROS) 诱导 A549 和 H1975 细胞凋亡。该研究为开发新的抗癌药物提供了策略。