Oridonin ring A-based diverse constructions of enone functionality

Identification of novel dienone analogues effective for highly aggressive breast cancer by inducing apoptosis

Chunyong Ding, Yusong Zhang, Haijun Chen, Zhengduo Yang, Christopher Wild, Na Ye, Corbin D. Ester, Ailian Xiong, Mark White, Qiang Shen, Jia Zhou

Research output: Contribution to journalArticle

45 Citations (Scopus)

Abstract

Oridonin (1) has attracted considerable attention in recent years because of its unique and safe anticancer pharmacological profile. Nevertheless, it exhibits moderate to poor effects against highly aggressive cancers including triple-negative and drug-resistant breast cancer cells. Herein, we report the rational design and synthesis of novel dienone derivatives with an additional α,β-unsaturated ketone system diversely installed in the A-ring based on this class of natural scaffold that features dense functionalities and stereochemistry-rich frameworks. Efficient and regioselective enone construction strategies have been established. Meanwhile, a unique 3,7-rearrangement reaction was identified to furnish an unprecedented dienone scaffold. Intriguingly, these new analogues have been demonstrated to significantly induce apoptosis and inhibit colony formation with superior antitumor effects against aggressive and drug-resistant breast cancer cells in vitro and in vivo while also exhibiting comparable or lower toxicity to normal human mammary epithelial cells in comparison with 1.

Original languageEnglish (US)
Pages (from-to)8814-8825
Number of pages12
JournalJournal of Medicinal Chemistry
Volume56
Issue number21
DOIs
StatePublished - Nov 14 2013

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Apoptosis
Breast Neoplasms
Ketones
Pharmaceutical Preparations
Breast
Epithelial Cells
Pharmacology
Neoplasms
oridonin
In Vitro Techniques

ASJC Scopus subject areas

  • Molecular Medicine
  • Drug Discovery

Cite this

Oridonin ring A-based diverse constructions of enone functionality : Identification of novel dienone analogues effective for highly aggressive breast cancer by inducing apoptosis. / Ding, Chunyong; Zhang, Yusong; Chen, Haijun; Yang, Zhengduo; Wild, Christopher; Ye, Na; Ester, Corbin D.; Xiong, Ailian; White, Mark; Shen, Qiang; Zhou, Jia.

In: Journal of Medicinal Chemistry, Vol. 56, No. 21, 14.11.2013, p. 8814-8825.

Research output: Contribution to journalArticle

Ding, Chunyong ; Zhang, Yusong ; Chen, Haijun ; Yang, Zhengduo ; Wild, Christopher ; Ye, Na ; Ester, Corbin D. ; Xiong, Ailian ; White, Mark ; Shen, Qiang ; Zhou, Jia. / Oridonin ring A-based diverse constructions of enone functionality : Identification of novel dienone analogues effective for highly aggressive breast cancer by inducing apoptosis. In: Journal of Medicinal Chemistry. 2013 ; Vol. 56, No. 21. pp. 8814-8825.
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