Osorio Alex A, López Manuel R, Jiménez Ignacio A, Moujir Laila M, Rodríguez Matías L, Bazzocchi Isabel L
Instituto Universitario de Bio-Orgánica Antonio González, Departamento de Química Orgánica and Instituto Canario de Investigación del Cáncer, Universidad de La Laguna, Avenida Astrofísico Francisco Sánchez 2, 38206 La Laguna, Tenerife, Spain.
Departamento de Microbiología y Biología Celular, Universidad de La Laguna, Avenida Astrofísico Francisco Sánchez s/n, 38206 La Laguna, Tenerife, Spain.
Phytochemistry. 2014 Sep;105:60-7. doi: 10.1016/j.phytochem.2014.06.009. Epub 2014 Jul 7.
In the present study, we report six cardiac glycosides (1-6) along with four known ones (7-10) isolated from the leaves and fruits of Elaeodendron orientale. Their stereostructures were elucidated on the basis of spectroscopic analysis, including 1D and 2D NMR, and the absolute configuration of 1 was determined by X-ray diffraction analysis. The compounds were evaluated for growth inhibitory activity against a panel of human cancer cell lines, HeLa, A-549, MCF-7 and HL-60, and normal Vero cells. Four compounds from this series (5 and 7-9, IC50 values ranging from 0.01 to 0.07μM) exhibited cytotoxicity against three of the cancer cell lines assayed that was similar to or higher than the well-known therapies digoxin and digitoxigenin. Taking into account the narrow safety range of cardiac glycosides used in clinic, this series shows a selectivity index higher than 3 for three of the cancer cell lines assayed, increasing their interest for further study.
在本研究中，我们报道了从东方油丹的叶和果实中分离得到的6种强心苷（1-6）以及4种已知化合物（7-10）。基于包括一维和二维核磁共振在内的光谱分析阐明了它们的立体结构，并通过X射线衍射分析确定了化合物1的绝对构型。对这些化合物针对一组人类癌细胞系（HeLa、A-549、MCF-7和HL-60）以及正常Vero细胞进行了生长抑制活性评估。该系列中的4种化合物（5以及7-9，IC50值范围为0.01至0.07μM）对所检测的三种癌细胞系表现出细胞毒性，其毒性与著名疗法地高辛和洋地黄毒苷相似或更高。考虑到临床使用的强心苷安全范围较窄，该系列对所检测的三种癌细胞系的选择性指数高于3，这增加了它们进一步研究的价值。
