Highly aggressive and drug-resistant breast cancer remains an unmet medical need and represents an important clinical challenge. Oridonin, isolated from the herb rabdosia rubescens that is often used in Chinese traditional medicine, has attracted considerable attention in recent years due to its remarkably unique and safe anticancer pharmacological profile. Nevertheless, it is not very effective against highly aggressive and drug-resistant breast cancer cells such as triple-negative MDA-MB-231. Herein, we disclose our facile and efficient synthetic approaches to generating novel oridonin dienone analogues with the enone functionality diversely installed in the A-ring through a series of selective functional group transformations starting from the natural product. These new analogues have demonstrated superior anticancer effects against aggressive and drug-resistant breast cancer in vitro and in vivo, while exhibiting comparable or less toxicity to normal human mammary epithelial cells in comparison with oridonin.

Oridonin ring A-based diverse constructions of enone functionality: Identification of novel dienone analogs for treatment of highly aggressive breast cancer

246th National Meeting (2013)

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