本文合成了一系列新型香豆素衍生物1-15,并评价了它们对A549细胞的抗癌活性。多数衍生物表现出中等程度的抑制活性。其中,衍生物2、13-15具有显著的生物活性,IC50值范围为4.7±0.7至17.9±2.1 μM。衍生物13在体外对A549细胞具有显著的抑制活性,IC50值为4.7±0.7 µM。对衍生物13进行网络药理学研究,共得到166个交集靶点。PPI网络分析表明,EGFR是关键靶点;富集性分析提示,衍生物13可能通过多靶点调控与细胞存活及增殖相关的关键信号通路,从而发挥抗肺癌的作用。使用分子对接进行验证发现,衍生物13对EGFR的对接得分为-7.93 kcal/mol。分子对接结果显示,衍生物13能够与EGFR蛋白的Ser-784、Arg-748和Lys-754残基形成相互作用,这可能是其发挥调控作用的潜在机制。同时,衍生物13显著影响了A549细胞周期,使之阻滞于G0/G1期。研究结果表明,衍生物13有望成为抗非小细胞肺癌的先导化合物。
A series of novel coumarin derivatives 1-15 were synthesized and evaluated for their anticancer activity against A549 cell. Most derivatives showed moderate inhibitory activities. Among them, derivatives 2, 13-15 presented remarkable bioactivities with IC50 values range from 4.7±0.7 to 17.9±2.1 μM. Derivative 13 exhibited remarkable inhibitory activity against A549 (IC50 = 4.7±0.7 µM) in vitro. Network pharmacology analysis of derivative 13 yielded a total of 166 intersecting targets. The PPI network identified EGFR as a key target, and enrichment analysis suggested that derivative 13 may exert its anti-lung cancer effects through multi target regulation of key signaling pathways associated with cell survival and proliferation. Docking analysis showed that derivative 13 exhibited a docking score of -7.93 kcal/mol for EGFR. It was found to exert potential regulatory effects on the EGFR by interacting with Ser-784, Arg-748, and Lys-754 residues. Additionally, derivative 13 significantly affected the cell cycle of A549 cells, inducing G0/G1-phase arrest. Thus, these results suggest that derivative 13 is a promising lead compound for the treatment of non-small cell lung cancer.
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