Oleanolic acid (OA) and its semi-synthetic derivatives have been reported to have a wide range of biological activities. The introduction of electrophilic Michael acceptor group can increase the reactivity of OA to cellular targets and thus improve the anti-tumor activity. In this work, a series of novel α,β-unsaturated carbonyl derivatives of OA were designed and synthesized. Their in vitro cytotoxic activity against MCF-7, HepG2 and HeLa cells were tested. Most derivatives exhibited improved cell growth inhibitory activity, especially for 3d with an IC₅₀ of 0.77 μM in MCF-7 cells. Moreover, 3d inhibited the migration of MCF-7 and HeLa cells at the concentration of 4 μM. Flow cytometric analysis revealed that 3d induced cell apoptosis and S phase arrest in a concentration-dependent manner. Western blotting experiment demonstrated that 3d inhibited the phosphorylation of AKT and mTOR. These results suggest that this series of OA derivatives bearing exocyclic methylene ketone pharmacophore are promising anticancer agents as potential PI3K/AKT/mTOR pathway inhibitors.

齐墩果酸（OA）及其半合成衍生物据报道具有广泛的生物活性。亲电迈克尔基团的引入可以增加OA对细胞靶标的反应性，从而提高抗肿瘤活性。在这项工作中，设计并合成了一系列新颖的OA的α，β-不饱和羰基衍生物。测试了它们对MCF-7，HepG2和HeLa细胞的体外细胞毒性活性。大多数衍生物表现出改善的细胞生长抑制活性，尤其是对于3d而言，MCF-7细胞的IC ₅₀为0.77μM。此外，3d在浓度为4μM时抑制了MCF-7和HeLa细胞的迁移。流式细胞仪分析显示3d诱导细胞凋亡和S期停滞以浓度依赖的方式。Western印迹实验表明3d抑制了AKT和mTOR的磷酸化。这些结果表明，该系列带有环外亚甲基酮药效基团的OA衍生物有望作为潜在的PI3K / AKT / mTOR途径抑制剂。