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6,7-seco-ent-kauranoids derived from oridonin as potential anticancer agents

Xu, Shengtao; Yao, Hong; Hu, Mei; Li, Dahong; Zhu, Zheying; Xie, Weijia; Yao, Hequan; Wu, Liang; Chen, Zhe-Sheng; Xu, Jinyi

Authors

Shengtao Xu

Hong Yao

Mei Hu

Dahong Li

ZHEYING ZHU Zheying.Zhu@nottingham.ac.uk
Associate Professor in International Pharmacy and Traditional Medicines

Weijia Xie

Hequan Yao

Liang Wu

Zhe-Sheng Chen

Jinyi Xu



Abstract

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.

Citation

Xu, S., Yao, H., Hu, M., Li, D., Zhu, Z., Xie, W., …Xu, J. (in press). 6,7-seco-ent-kauranoids derived from oridonin as potential anticancer agents. Journal of Natural Products, https://doi.org/10.1021/acs.jnatprod.7b00057

Journal Article Type Article
Acceptance Date Sep 4, 2017
Online Publication Date Sep 13, 2017
Deposit Date Sep 18, 2017
Publicly Available Date Sep 14, 2018
Journal Journal of Natural Products
Electronic ISSN 1520-6025
Publisher Journal of Natural Products
Peer Reviewed Peer Reviewed
DOI https://doi.org/10.1021/acs.jnatprod.7b00057
Public URL http://eprints.nottingham.ac.uk/id/eprint/46459
Publisher URL http://pubs.acs.org/doi/abs/10.1021/acs.jnatprod.7b00057
Copyright Statement Copyright information regarding this work can be found at the following address: http://eprints.nottingh.../end_user_agreement.pdf

Files

JNP-accepted manuscript.pdf (1.2 Mb)
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Copyright Statement
Copyright information regarding this work can be found at the following address: http://eprints.nottingham.ac.uk/end_user_agreement.pdf





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