Seven new polyketide compounds, four naphthoquinone derivatives, neofusarubins A–D (1, 3, 5, and 18) and three graminin-like compounds, fusofuranones A–C (19–21), together with 14 known naphthoquinone derivatives, were isolated from the solid fermentation of Fusarium solani, an endophytic fungus obtained from medicinal plant as tea, Camellia chrysantha. The structures of new compounds were elucidated based on chemical evidence and spectral data analysis (1D and 2D-NMR, HR-ESI-MS, ECD, SC-XRD). Among the isolated compounds tested, 2-acetonyl-3-methyl-5-hydroxy-7-methoxy-naphthazarin (11) exhibited the most potent inhibitory activity against pancreatic cancer in PANC-1, MiaPaCa-2, and BxPC-3 cells. Network pharmacology analysis revealed that compound 11 inhibited cell proliferation and promotion of apoptosis by targeting epidermal growth factor receptor (EGFR), which were confirmed by cellular thermal shift assay (CETSA), microscale thermophoresis (MST) and EGFR stably knockdown cells model assay, respectively. In addition, molecular mechanism studies in vitro showed that 11 could suppress the growth of pancreatic cancer cells by targeting EGFR and effectively inhibit downstream PI3K/Akt signaling pathway. Collectively, these findings provide a new EGFR targeting natural product for the treatment of pancreatic cancer.

中文翻译：

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来自内生真菌 Fusarium solani 的萘醌衍生物通过靶向 EGFR 介导的 PI3K/Akt 通路诱导胰腺癌细胞凋亡


从茄镰刀菌（Fusarium solani）的固体发酵中分离出 7 种新的聚酮化合物、4 种萘醌衍生物、新褐藻红素 A-D（1、3、5 和 18）和 3 种禾本科样化合物、梭索呋喃酮 A-C （19-21） 以及 14 种已知的萘醌衍生物，从茄镰刀菌（Fusarium solani）的固体发酵中分离出来，镰刀菌是一种从茶叶植物山茶中获得的内生真菌.基于化学证据和光谱数据分析 （1D 和 2D-NMR、HR-ESI-MS、ECD、SC-XRD） 阐明了新化合物的结构。在测试的分离化合物中，2-乙酰基-3-甲基-5-羟基-7-甲氧基-萘萘素 （11） 在 PANC-1、MiaPaCa-2 和 BxPC-3 细胞中表现出对胰腺癌最有效的抑制活性。网络药理学分析显示，化合物 11 通过靶向表皮生长因子受体 （EGFR） 抑制细胞增殖和促进细胞凋亡，分别通过细胞热转移试验 （CETSA） 、微量热泳 （MST） 和 EGFR 稳定敲低细胞模型测定证实。此外，体外分子机制研究表明，11 可通过靶向 EGFR 抑制胰腺癌细胞的生长，有效抑制下游 PI3K/Akt 信号通路。总的来说，这些发现为治疗胰腺癌提供了一种新的 EGFR 靶向天然产物。