Structurally unique 6,7-seco-ent-kaurenes, which are widely distributed in the genus Isodon, have attracted considerable attention because of their antitumor activities. Previously, a convenient conversion of commercially available oridonin (1) to 6,7-seco-ent-kaurenes was developed. Herein, several novel spiro-lactone-type ent-kaurene derivatives bearing various substituents at the C-1 and C-14 positions were further designed and synthesized from the natural product oridonin. Moreover, a number of seven-membered C-ring-expanded 6,7-seco-ent-kaurenes were also identified for the first time. It was observed that most of the spiro-lactone-type ent-kaurenes tested markedly inhibited the proliferation of cancer cells, with an IC₅₀ value as low as 0.55 μM. An investigation on its mechanism of action showed that the representative compound 7b affected the cell cycle and induced apoptosis at a low micromolar level in MCF-7 human breast cancer cells. Furthermore, compound 7b inhibited liver tumor growth in an in vivo mouse model and exhibited no observable toxic effects. Collectively, the results warrant further preclinical investigations of these spiro-lactone-type ent-kaurenes as potential novel anticancer agents.

中文翻译：

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6,7- Seco- ENT -Kauranoids从冬凌草甲素推导出潜在的抗癌药物

结构独特的6,7- seco- ENT -kaurenes，广泛分布于属香茶，已经吸引了，因为他们的抗肿瘤活性的极大关注。此前，市售冬凌草甲素（一种方便的转化1）至6,7- seco- ENT -kaurenes被开发。在此，从天然产物冬凌草甲素中进一步设计和合成了几种在C-1和C-14位置带有各种取代基的螺内酯型对映体-新戊烯衍生物。此外，一系列的7元C-环扩展-6,7- seco- ENT -kaurenes也被鉴定为第一次。据观察，大多数螺内酯型耳鼻喉科测试的β-天竺葵烯酮显着抑制癌细胞的增殖，IC ₅₀值低至0.55μM 。对其作用机理的研究表明，代表性化合物7b在MCF-7人乳腺癌细胞中以低微摩尔水平影响细胞周期并诱导凋亡。此外，化合物7b在体内小鼠模型中抑制肝肿瘤生长，并且没有显示出可观察到的毒性作用。总的来说，这些结果值得对作为潜在的新型抗癌药的这些螺内酯型ENT-脲酮进行进一步的临床前研究。