School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, 510006, China.
Org Biomol Chem. 2020 Jul 15;18(27):5130-5136. doi: 10.1039/d0ob00666a.
Spiroconyone A (1), the first rearranged phytosterol featuring an unusual spiro [5,6] ring system, and nine known compounds (2-10) were isolated from the aerial parts of Conyza japonica. The structure of 1 was elucidated through spectroscopic methods, and its absolute configuration was determined by single-crystal X-ray diffraction analysis. Enzyme-based assay revealed that spiroconyone A showed weak TDP1 inhibition and compounds 7 and 10 showed TDP1 inhibition with IC50 values of 36 μM and 16 μM, respectively. MTT assay indicated that 7 and 10 showed a strong synergistic effect with the clinical TOP1 inhibitor topotecan in MCF-7 cells. Compound 5 displayed the most potent cytotoxicity against MCF-7 cells with a GI50 value of 3.3 μM. Furthermore, a hypothetical biosynthetic pathway for 1 was proposed. This work provides valuable information that the secondary metabolites from Conyza japonica could be developed as anticancer agents.
从菊科植物野茼蒿的地上部分分离得到了螺环酮 A（1），这是第一个具有不寻常螺环[5,6]体系的重排植物甾醇，以及 9 种已知化合物（2-10）。通过光谱方法阐明了 1 的结构，并通过单晶 X 射线衍射分析确定了其绝对构型。基于酶的测定表明，螺环酮 A 对 TDP1 表现出较弱的抑制作用，化合物 7 和 10 对 TDP1 的抑制作用，IC50 值分别为 36 μM 和 16 μM。MTT 分析表明，7 和 10 与临床 TOP1 抑制剂拓扑替康在 MCF-7 细胞中具有很强的协同作用。化合物 5 对 MCF-7 细胞表现出最强的细胞毒性，GI50 值为 3.3 μM。此外，还提出了 1 的假设生物合成途径。这项工作提供了有价值的信息，即野茼蒿的次生代谢产物可开发为抗癌药物。
