Department of Medicinal Chemistry, China Pharmaceutical University, Nanjing 211198, China.
School of Traditional Chinese Pharmacy, China Pharmaceutical University, Nanjing 211198, China.
Bioorg Chem. 2021 Jul;112:104941. doi: 10.1016/j.bioorg.2021.104941. Epub 2021 Apr 24.
A series of 1,2-didehydro-3-ox-andrographolide derivatives based on two Michael acceptors were designed, synthesized and evaluated for their anticancer activity against two human cancer cell lines (HCT116 and MCF-7). All tested compounds exhibited significant growth inhibitory effect on HCT116 and moderate to good inhibitory effect on MCF-7 cell proliferation. Compound 10b displayed the best inhibitory activities against both HCT116 and MCF-7 cell lines, with IC values of 2.49 and 7.80 μM respectively. Preliminary anticancer mechanistic investigation was performed in terms of the cell cycle arrest and cell apoptosis assays of compound 10b against HCT116 using flow cytometry, and the results indicated that 10b blocked the proliferation of HCT116 cells by inducing cell apoptosis in a concentration-dependent manner and arresting cell cycle in G/M phase.
基于两个迈克尔受体，设计、合成了一系列 1,2-二去氢-3-氧穿心莲内酯衍生物，并对其进行了抗两种人癌细胞系（HCT116 和 MCF-7）的抗癌活性评价。所有测试的化合物对 HCT116 表现出显著的生长抑制作用，对 MCF-7 细胞增殖具有中度至良好的抑制作用。化合物 10b 对 HCT116 和 MCF-7 细胞系均表现出最佳的抑制活性，IC 值分别为 2.49 和 7.80 μM。通过流式细胞术对化合物 10b 进行了针对 HCT116 的细胞周期阻滞和细胞凋亡分析，初步探讨了抗癌机制，结果表明，10b 通过诱导细胞凋亡和使细胞周期阻滞在 G/M 期，以浓度依赖的方式阻断 HCT116 细胞的增殖。
