School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 510006, People's Republic of China.
School of Chemistry, Sun Yat-sen University, Guangzhou 510006, People's Republic of China.
Bioorg Chem. 2021 Oct;115:105269. doi: 10.1016/j.bioorg.2021.105269. Epub 2021 Aug 16.
By tracing the C NMR resonances for carbonyls and enols, four new oxidized phomaligol derivatives, phomaligols F-I (1-4), along with seven known compounds (5-11) were isolated from the culture of the fungus Aspergillus flavus BB1 isolated from the marine shellfish Meretrix meretrix collected on Hailing Island, Yangjiang, China. The chemical structures and the absolute configurations of the new compounds were elucidated by MS, NMR, ECD, optical rotation, and C NMR calculations. Compounds 1 and 2 represent the first examples of phomaligol derivatives that contain an unusual bicyclic skeleton. All isolated compounds were tested for their cytotoxic activity. Among them, sporogen-AO 1 (8) showed potent inhibitory activity against the cancer cell lines A549, H1299, SK-BR-3, and HCT116 with IC values of 0.13, 0.78, 1.19, and 1.32 μM, respectively. Phomaligol G (2) displayed cytotoxic activity against the A549 and H1299 cell lines with IC values of 46.86 and 51.87 μM respectively. Additionally, phomaligol H (3) demonstrated cytotoxic activity against the A549 cell line with an IC value of 65.53 μM. Mechanistic studies of compound 8 showed that it induced apoptosis of HCT116 cells in a dose-dependent manner.
从海洋贝类 Meretrix meretrix 中分离得到的中国阳江海陵岛的真菌 Aspergillus flavus BB1 的培养物中，通过追踪羰基和烯醇的 C NMR 共振，分离得到了四个新的氧化 phomaligol 衍生物，phomaligols F-I（1-4），以及七个已知化合物（5-11）。通过 MS、NMR、ECD、旋光和 C NMR 计算，阐明了新化合物的化学结构和绝对构型。化合物 1 和 2 代表了含有不寻常双环骨架的 phomaligol 衍生物的第一个例子。所有分离得到的化合物均进行了细胞毒性活性测试。其中，sporogen-AO 1（8）对 A549、H1299、SK-BR-3 和 HCT116 癌细胞系具有很强的抑制活性，IC 值分别为 0.13、0.78、1.19 和 1.32μM。Phomaligol G（2）对 A549 和 H1299 细胞系的细胞毒性活性分别为 46.86 和 51.87μM。此外，phomaligol H（3）对 A549 细胞系的细胞毒性活性为 65.53μM。化合物 8 的机制研究表明，它以剂量依赖的方式诱导 HCT116 细胞凋亡。
