Oridonin Ring A-Based Diverse Constructions of Enone Functionality: Identification of Novel Dienone Analogues Effective for Highly Aggressive Breast Cancer by Inducing Apoptosis

摘要: 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 drug-resistant breast cancer cells. Herein, we report the rational design synthesis novel dienone derivatives with an additional α,β-unsaturated ketone system diversely installed A-ring based on this class natural scaffold that features dense functionalities stereochemistry-rich frameworks. Efficient regioselective enone construction strategies have been established. Meanwhile, a 3,7-rearrangement reaction was identified furnish unprecedented scaffold. Intriguingly, these new analogues demonstrated significantly induce apoptosis inhibit colony formation superior antitumor cells vitro vivo while also exhibiting comparable or lo...