6,7-Seco-<i>ent</i>-Kauranoids Derived from Oridonin as Potential Anticancer Agents

Published on 2017-09-13T13:50:44Z (GMT) by
Structurally unique 6,7-seco-<i>ent</i>-kaurenes, which are widely distributed in the genus <i>Isodon</i>, have attracted considerable attention because of their antitumor activities. Previously, a convenient conversion of commercially available oridonin (<b>1</b>) to 6,7-seco-<i>ent</i>-kaurenes was developed. Herein, several novel spiro-lactone-type <i>ent</i>-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-<i>ent</i>-kaurenes were also identified for the first time. It was observed that most of the spiro-lactone-type <i>ent</i>-kaurenes tested markedly inhibited the proliferation of cancer cells, with an IC<sub>50</sub> value as low as 0.55 μM. An investigation on its mechanism of action showed that the representative compound <b>7b</b> affected the cell cycle and induced apoptosis at a low micromolar level in MCF-7 human breast cancer cells. Furthermore, compound <b>7b</b> 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 <i>ent</i>-kaurenes as potential novel anticancer agents.

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Xu, Shengtao; Yao, Hong; Hu, Mei; Li, Dahong; Zhu, Zheying; Xie, Weijia; Yao, Hequan; Wu, Liang; Chen, Zhe-Sheng; Xu, Jinyi (2017): 6,7-Seco-ent-Kauranoids Derived from Oridonin as Potential Anticancer Agents. ACS Publications. Collection.