Eight rocaglaol derivatives with good cytotoxic activity (IC₅₀: 0.013 ∼ 5.82 μM) were isolated from Aglaia odorata. Then, a series of novel derivatives with modifications on C3 of rocaglaol were designed, synthesized, and screened for their antitumor activities against three tumor cell lines (HEL, MDA-MB-231, and HCT116). A total of 44 derivatives exhibited significant cytotoxic activity with IC₅₀ values lower than 1 μM. In particular, four derivatives (14, 20, 22j, and 22r) exhibited the best cytotoxic activity against HCT116 cells, with an IC₅₀ value of 70 nM. Compound 22r with relatively low toxicity against normal cells and the best cytotoxic activity against HCT116 cells was selected for further study. Subsequent cellular mechanism studies showed that compound 22r induced apoptosis and G1 cell cycle arrest in HCT116 cells. Moreover, compound 22r inhibited both the Wnt/β-catenin and MAPK signaling pathways via key proteins, such as the phosphorylation of p38 and JNK, GSK-3β, Axin-2, etc. Therefore, our present results suggest that compound 22r is a potential candidate for developing novel anti-colorectal cancer agents in the future.

从Aglaia odorata中分离出八种具有良好细胞毒活性的罗格劳醇衍生物 (IC ₅₀ : 0.013 ∼ 5.82 μM) 。然后，设计、合成了一系列对罗格劳醇 C3 进行修饰的新型衍生物，并筛选了它们对三种肿瘤细胞系（HEL、MDA-MB-231 和 HCT116）的抗肿瘤活性。共有 44 种衍生物表现出显着的细胞毒活性，IC ₅₀值低于 1 μM。特别是，四种衍生物（14、20、22j和22r）对HCT116 细胞表现出最佳的细胞毒活性，IC 50值为 70 nM _。化合物22r选择对正常细胞毒性相对较低且对 HCT116 细胞具有最佳细胞毒活性的药物进行进一步研究。随后的细胞机制研究表明，化合物22r在 HCT116 细胞中诱导细胞凋亡和 G1 细胞周期停滞。此外，化合物22r通过关键蛋白抑制 Wnt/β-catenin 和 MAPK 信号通路，如 p38 和 JNK、GSK-3β、Axin-2 等的磷酸化。因此，我们目前的结果表明，化合物22r是一种未来开发新型抗结直肠癌药物的潜在候选者。