Abstract

Five 3-formyl-2-arylbenzofuran derivatives, including three new compounds (1-3) and two known analogues (4-5), were identified from the 95% EtOH extract of Itea yunnanensis. Extensive spectroscopic analyses were performed for the structure elucidation of all new benzofurans, and single-crystal X-ray diffraction analyses were further employed for the structure verification of iteafuranals C (1) and D (2). In MTT assay, iteafuranal E (3) and iteafuranal A (4) displayed significant growth inhibition effect on SK-Hep-1 cells with IC₅₀ values of 5.365 μM and 6.013 μM, respectively. The colony formation assay of 3 and 4 further confirmed their remarkable inhibitory effect on cell growth. Preliminary mechanism study demonstrated that 3 remarkably down-regulated the phosphorylation level of ERK, which suggested 3 could inhibit cell growth and induce apoptosis of SK-Hep-1 cells by blocking RAS/RAF/MEK/ERK signaling pathway. This study highlighted the potential of 3-fomyl-2-benzofuran derivatives as novel lead compounds to treat Hepatocellular carcinoma.

摘要

从云南红茶的 95% EtOH 提取物中鉴定出五种3-甲酰基-2-芳基苯并呋喃衍生物，包括三种新化合物 ( 1-3 )和两种已知类似物 ( 4-5 )。对所有新苯并呋喃的结构进行了广泛的光谱分析，并进一步采用单晶X射线衍射分析对iteafuranals C( 1 )和D( 2 )的结构进行了验证。在MTT试验中，iteafuranal E ( 3 ) 和iteafuranal A ( 4 ) 对SK-Hep-1细胞具有显着的抑制作用，IC ₅₀值分别为 5.365 μM 和 6.013 μM。3和4的集落形成试验进一步证实了它们对细胞生长的显着抑制作用。初步机制研究表明，3显着下调ERK的磷酸化水平，提示3可通过阻断RAS/RAF/MEK/ERK信号通路抑制细胞生长，诱导SK-Hep-1细胞凋亡。本研究强调了 3-甲酰-2-苯并呋喃衍生物作为治疗肝细胞癌的新型先导化合物的潜力。