壮药古羊藤中一个新的倍半萜

A new sesquiterpene from Zhuang Medicine Streptocaulon juventas

关键词:  古羊藤，马莲鞍属，古羊藤二酮，强心苷，倍半萜，细胞毒活性

Key words:  streptocaulon juventas, streptocaulon, strejuvdione, cardiac glycosides, sesquiterpene, cytotoxic activity

摘要:

为探究壮药古羊藤[Streptocaulon juventas (Lour.) Merr.]的化学成分及其细胞毒活性，该研究采用硅胶、SephadexLH-20、C18中低压和半制备高效液相色谱等方法对古羊藤中化学成分进行分离，通过理化性质以及MS、NMR、单晶X射线衍射等方法鉴定化合物结构；运用MTS法检测单体化合物对5种肿瘤细胞增殖的抑制活性。结果从古羊藤中分离鉴定出16个化合物，分别为古羊藤二酮 A（1*）、6-姜烯酚（2）、莪术烯醇（3）、curcuzedoalide（4）、16-dehydropregnenolone（5）、neridienone A（6）、12β-hydroxy-pregna-4,16-diene-3,20-dione（7）、杠柳苷元（8）、acovenosigenin A（9）、洋地黄毒苷元（10）、digitoxigenin-3-O-β-D-glucoside（11）、杠柳苷元葡萄糖苷（12）、8-hydroxypinoresinol（13）、布卢门醇 A（14）、布卢门醇 B（15）和东莨菪内酯（16）。其中1*为新化合物，2-4、6、7、13-15为首次从该植物中分离得到。体外活性实验结果显示化合物2、6-12对人白血病HL-60、肺癌 A549、肝癌SMMC-7721、结肠癌SW480细胞具有较好的增殖抑制活性，其IC50值分别为0.97~23.77、0.87~29.43、0.07~13.77、0.09~16.47 μmol·L-1。化合物2、6-10、12对乳腺癌MDA-MB-231具有增殖抑制活性，其IC50值为0.07~27.73 μmol·L-1。该研究结果丰富了古羊藤的化学成分，可为抗肿瘤活性研究提供参考。

Abstract:

This study aimed to investigate the chemical constituents of Streptocaulon juventas (Lour.) Merr., a plant used in Zhuang medicine, and evaluate their cytotoxic activities. Chemical isolation was performed using a combination of chromatographic techniques, including silica gel column chromatography, Sephadex LH-20, Flash C18 and semi-preparative high-performance liquid chromatography. Structural elucidation of the isolated compounds was achieved through comprehensive analysis of physicochemical properties and spectroscopic data, such as mass spectrometry (MS), nuclear magnetic resonance spectroscopy (NMR) and X-ray single crystal diffraction. The cytotoxic activities of the isolated monomeric compounds against five human tumor cell lines were assessed using the MTS assay to determine their inhibitory effects on cell proliferation. The results were as follows: (1) Sixteen compounds were successfully isolated and identified from S. juventas, which were strejuvdione A (1*), 6-shogoal (2), curcumenol (3), curcuzedoalide (4), 16-dehydropregnenolone (5), neridienone A (6), 12β-hydroxy-pregna-4,16-diene-3,20-dione (7), periplogenin (8), acovenosigenin A (9), digitoxigenin (10), digitoxigenin-3-O-β-D-glucoside (11), periplogenin glucoside (12), 8-hydroxypinoresinol (13), blumenol A (14), blumenol B (15), and scopoletin (16). Notably, Compound 1* is a new compound. Furthermore, compounds 2-4, 6, 7, and 13-15 were isolated from this plant for the first time. (2) Cytotoxicity screening revealed significant antiproliferative activities for specific compounds. Compounds 2, 6-12 exhibited significant proliferation inhibitory activities against leukemia HL-60, lung cancer A549, liver cancer SMMC-7721, and colon cancer SW480 cell lines, with IC50 values ranging from 0.97-23.77, 0.87-29.43, 0.07-13.77, and 0.09-16.47 μmol·L?1. respectively. Compounds 2, 6-10 and 12 demonstrated inhibitory effects on breast cancer MDA-MB-231 cells, with IC50 values between 0.07-27.73 μmol·L?1. The phytochemical investigation significantly enriches the chemical diversity of S. juventas, identifying one novel compound and reporting eight constituents isolated from this plant for the first time. The in vitro cytotoxicity results provide compelling evidence that several isolated compounds, particularly cardenolides like periplogenin (8), digitoxigenin (10), and their glycosides (11, 12) possess marked antiproliferative effects. These findings underscore the potential of S. juventas as a valuable source of cytotoxic agents and offer a substantial foundation for future research aimed at developing novel anticancer leads derived from Zhuang ethnomedicine. The structure-activity relationships observed warrant further mechanistic and in vivo studies.