1'-羟基-4',8,8'-三甲氧基-[2,2'-联萘]-1,4-二酮（化合物5）是最近在海洋真菌中发现的一种次级代谢产物，具有良好的细胞毒性和抗癌潜力。然而，关于其衍生物的抗癌活性和生物学机制的知识仍然有限。在此，设计、合成了一系列新型萘醌-萘酚衍生物，并评估了它们对不同来源癌细胞的抗癌活性。其中，醌基邻位具有氧代丙基的化合物13对HCT116、PC9和A549细胞表现出最强的抑制作用，IC50值从5.27降低至1.18μM（增加4.5倍）。与化合物 5 相比，分别增加 6.98 至 0.57μM（增加 12 倍）和 5.88 至 2.25μM（增加 2.6 倍）。进一步的机制研究表明，化合物 13 通过增加 cleaved caspase- 的表达水平，显着诱导细胞凋亡。 3 并通过下调 EGFR/PI3K/Akt 信号通路减少 Bcl-2 蛋白，从而抑制 HCT116 和 PC9 细胞的增殖。目前的研究结果表明，这种新型萘醌-萘酚衍生物可能具有作为抗癌治疗先导药物的潜力。

1'-Hydroxy-4',8,8'-trimethoxy-[2,2'-binaphthalene]-1,4-dione (compound 5), a secondary metabolite recently discovered in marine fungi, demonstrates promising cytotoxic and anticancer potential. However, knowledge regarding the anticancer activities and biological mechanisms of its derivatives remains limited. Herein, a series of novel naphthoquinone-naphthol derivatives were designed, synthesised, and evaluated for their anticancer activity against cancer cells of different origins. Among these, Compound 13, featuring an oxopropyl group at the ortho-position of quinone group, exhibited the most potent inhibitory effects on HCT116, PC9, and A549 cells, with IC50 values decreasing from 5.27 to 1.18 μM (4.5-fold increase), 6.98 to 0.57 μM (12-fold increase), and 5.88 to 2.25 μM (2.6-fold increase), respectively, compared to compound 5. Further mechanistic studies revealed that compound 13 significantly induced cell apoptosis by increasing the expression levels of cleaved caspase-3 and reducing Bcl-2 proteins through downregulating the EGFR/PI3K/Akt signalling pathway, leading to the inhibition of proliferation in HCT116 and PC9 cells. The present findings suggest this novel naphthoquinone-naphthol derivative may hold potential as an anticancer therapeutic lead.