Cytotoxic Cyclodepsipeptides and Cyclopentane Derivatives from a Plant-Associated Fungus Fusarium sp.

In this work, four new cyclodepsipeptides, fusarihexins C–E (1–3) and enniatin Q (4), four new cyclopentane derivatives, fusarilins A–D (5–8), together with eight known compounds (9–16), were isolated from cultures of the endophytic fungus Fusarium sp. The structures of the isolated compounds were elucidated by analysis of HRMS and NMR spectroscopic data. The absolute configurations were determined using Marfey’s method, a modified Mosher’s method, single-crystal X-ray diffraction analysis, and ECD analysis. The antitumor activities of the isolated compounds in vitro were evaluated. Cyclodepsipeptides displayed cytotoxicities against the Huh-7, MRMT-1, and HepG-2 cell lines. Compounds 4, 9, 10, and 12 with IC50 values of 1.0–9.1 μM exhibited the most potent cytotoxicities against the three cell lines as compared to the positive control-5-fluorouracil. Compounds 1–3 and 11 exhibited moderate cytotoxic activities (IC50 values of 10.7–20.1 μM).

本研究从内生真菌镰孢属（Fusarium sp.）的培养物中，分离得到4个新型环缩肽类化合物（cyclodepsipeptides），包括fusarihexins C~E（1~3）与enniatin Q（4）；4个新型环戊烷衍生物fusarilins A~D（5~8），以及8个已知化合物（9~16）。通过高分辨质谱（HRMS）与核磁共振波谱（NMR）谱学数据分析，阐明了所有分离化合物的结构。采用马尔菲氏分析法（Marfey’s method）、改进的莫舍法（Mosher’s method）、单晶X射线衍射分析及电子圆二色谱（ECD）分析，确定了化合物的绝对构型。本研究对所有分离化合物的体外抗肿瘤活性进行了评价。环缩肽类化合物对Huh-7、MRMT-1及HepG-2细胞系均表现出细胞毒性。与阳性对照药5-氟尿嘧啶相比，化合物4、9、10和12的半数抑制浓度（IC50）为1.0~9.1 μM，对上述三种细胞系展现出最强的细胞毒活性；化合物1~3及11则表现出中等强度的细胞毒活性，其半数抑制浓度范围为10.7~20.1 μM。