目的 研究落花生根内生真菌Fusarium oxysporum LHS-P1-3的次级代谢产物及其生物活性。方法 使用硅胶色谱柱、高效液相色谱等对代谢粗提物进行分离纯化，采用质谱、核磁共振等方法测定化合物的结构，采用CCK-8法测试化合物的抗肿瘤细胞活性，使用表面等离子共振实验（surface plasmon resonance，SPR）研究化合物与胆固醇转运蛋白1（niemann-pick c1-like 1，NPC1L1）相互作用关系。结果 从落花生根内生真菌Fusarium oxysporum LHS-P1-3分离得到6个化合物，包括1个新化合物（1）与5个已知化合物：白僵菌素（2）、恩镰孢菌素I（3）、恩镰孢菌素MK1688（4）、恩镰孢菌素H（5）及恩镰孢菌素B（6）。化合物1～4对HepG2细胞和HeLa细胞的IC₅₀均小于10 μmol/L，化合物2～4则对HCT116细胞的IC₅₀小于10 μmol/L，SPR研究表明化合物2、4在20 μmol/L浓度下，可与NPC1L1蛋白相互作用。结论 化合物1为新的恩镰孢菌素类化合物，命名为恩镰孢菌素W。化合物1～5具有抗肿瘤活性，化合物2、4与NPC1L1蛋白存在相互作用，可能是NPC1L1蛋白的潜在抑制剂。

Objective To study the secondary metabolites and biological activities of the endophytic fungus Fusarium oxysporum LHS-P1-3 from Arachis hypogaea roots. Methods The crude metabolite was separated and purified by silica gel chromatography and high performance liquid chromatography. The structure of the compounds was determined by mass spectrometry and nuclear magnetic resonance. The inhibitory activity of the compounds on the proliferation of several tumor cells was tested by cell technology kit-8 (CCK-8). The interaction between compounds and niemann-pick c1-like 1(NPC1L1) protein was investigated by surface plasmon resonance (SPR) experiment. Results A total of six compounds were isolated from the endophytic fungus Fusarium oxysporum LHS-P1-3. There was one new compound enniatin W (1), and five known compounds beauverine (2), enniatin I (3), enniatin MK1688 (4), enniatin H (5) and enniatin B (6). Compounds 1—4 exhibited IC₅₀ values of less than 10 μmol/L on HepG2 and Hela cells, and compounds 2—4 also inhibited HCT116 activity with IC₅₀ values less than 10 μmol/L. SPR study demonsrated that compounds 2 and 4 could interact with NPC1L1 protein at a concentration of 20 μmol/L. Conclusion Compound 1 was a new enniatin benzaldehyde named enniatin W. Compounds 1—5 exhibited strong antitumor activity. Compounds 2 and 4 can interact with NPC1L1 protein and may be potential inhibitors of NPC1L1 protein.

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广西自然科学基金项目（2021GXNSFBA220040）；广西自然科学基金项目（2021GXNSFBA075036）；国家自然科学基金青年项目（82104034）；广西民族大学校级引进人才科研启动项目（2020KJQD09，2021KJQD09）；广西民族大学相思湖青年创新团队（2021RSCXSHQN01）；广西民族大学研究生创新计划（gxun-chxs2022086）