School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 510006, China.
School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 510006, China.
Bioorg Chem. 2018 Oct;80:511-518. doi: 10.1016/j.bioorg.2018.06.025. Epub 2018 Jun 20.
Nine new macrocyclic diterpenoids (1-9), jatromultones A-I, along with eight known analogues (10-17) were isolated from the trunks of Jatropha multifida. The structures of the new compounds, including their absolute configurations, were elucidated by combination of spectroscopic analysis, single crystal X-ray diffraction, Rh(OCOCF)-induced CD method, and chemical correlations. All compounds were screened for the cytotoxicity against five cancer cell lines, including one drug-resistant cell line, and seven compounds exhibited significant activity with IC values less than 10 μM. Compound 4 with IC values ranging from 2.69 to 6.44 μM toward all cell lines was selected for further mechanistic study, which showed that 4 could arrest cell cycle at G2/M phase and induce apoptosis. The brief structure-activity relationships (SARs) of these macrocyclic diterpenoids were also discussed.
从麻疯树的树干中分离得到了 9 个新的大环二萜（1-9），即 jatromultones A-I，以及 8 个已知类似物（10-17）。通过光谱分析、单晶 X 射线衍射、Rh(OCOCF)-诱导 CD 方法和化学相关等方法，确定了新化合物的结构，包括它们的绝对构型。对所有化合物进行了针对五种癌细胞系（包括一种耐药细胞系）的细胞毒性筛选，其中 7 种化合物表现出显著的活性，IC 值小于 10μM。选择具有对所有细胞系的 IC 值范围为 2.69 至 6.44μM 的化合物 4 进行进一步的机制研究，结果表明 4 可以将细胞周期阻滞在 G2/M 期并诱导细胞凋亡。还讨论了这些大环二萜的简要结构-活性关系（SARs）。
