State Key Laboratory of Medicinal Chemical Biology, College of Pharmacy and Tianjin Key Laboratory of Molecular Drug Research, Nankai University, Haihe Education Park, 38 Tongyan Road, Tianjin, 300353, People's Republic of China; Tianjin Key Laboratory of Molecular Drug Research, Tianjin International Joint Academy of Biomedicine, Tianjin, 300457, People's Republic of China.
State Key Laboratory of Medicinal Chemical Biology, College of Pharmacy and Tianjin Key Laboratory of Molecular Drug Research, Nankai University, Haihe Education Park, 38 Tongyan Road, Tianjin, 300353, People's Republic of China.
Phytochemistry. 2023 Oct;214:113802. doi: 10.1016/j.phytochem.2023.113802. Epub 2023 Jul 26.
Nine undescribed labdane diterpenoids (1-9) and one undescribed ent-halimane diterpenoid (10) were isolated from the aerial parts of Leonurus sibiricus, together with four known analogues (11-14) during our searching for naturally occurring antitumor agents. Their structures were established by detailed spectroscopic analyses and electronic circular dichroism analysis. Compound 4 possessed a rare 10-epi labdane scaffold. All compounds except 5 were evaluated for their inhibitory activities against interleukin (IL)-6-stimulated signal transducer and activator of transcription (STAT3) expression using a luciferase reporter assay. Compound 1 showed the most inhibitory effect with the IC value 20.31 μM. Compound 1 inhibited the activation of JAK2/STAT3 signal pathway through binding to Gln326 of STAT3 in CNE cells. The antiproliferative evaluation of compound 1 against CNE, CAL-27, A549 and PANC-1 cells demonstrated that CNE cells were the most sensitive to 1. Furthermore, compound 1 showed moderate efficacy in inhibiting cell migration, invasion, and epithelial-mesenchymal transition in CNE cells. In addition, compound 1 also promoted ferroptosis in CNE cells in a dose-dependent manner. These results suggest that compound 1 might be a potential candidate lead for treating nasopharyngeal carcinoma.
从益母草的地上部分分离得到了 9 个未描述的半日花烷二萜（1-9）和 1 个未描述的表海罂粟烷二萜（10），以及 4 个已知的类似物（11-14），这是我们在寻找天然抗肿瘤剂的过程中得到的。通过详细的光谱分析和电子圆二色性分析确定了它们的结构。化合物 4 具有罕见的 10-表半日花烷骨架。除了 5 之外，所有化合物都通过荧光素酶报告基因测定评估了它们对白细胞介素（IL）-6 刺激的信号转导和转录激活因子（STAT3）表达的抑制活性。化合物 1 表现出最显著的抑制效果，IC 值为 20.31 μM。化合物 1 通过与 CNE 细胞中 STAT3 的 Gln326 结合，抑制 JAK2/STAT3 信号通路的激活。对化合物 1 对 CNE、CAL-27、A549 和 PANC-1 细胞的增殖评估表明，CNE 细胞对 1 最敏感。此外，化合物 1 还表现出对 CNE 细胞迁移、侵袭和上皮间质转化的中度抑制作用。此外，化合物 1 还能以剂量依赖的方式在 CNE 细胞中促进铁死亡。这些结果表明，化合物 1 可能是治疗鼻咽癌的潜在候选药物。
