Many artemisinin derivatives have good inhibitory effects on malignant tumors. In this work, a novel series of artemisinin derivatives containing piperazine and fluorine groups were designed and synthesized and their structures were confirmed by ¹H-NMR, ¹³C-NMR and HRMS technologies. The in vitro cytotoxicity against various cancer cell lines was evaluated. Among the derivatives, compound 12h was found to exhibit not only the best activity against HCT-116 cells (IC₅₀= 0.12± 0.05μM), but also low toxicity against normal cell line L02 (IC₅₀= 12.46±0.10 μM. The mechanisms study revealed that compound 12h caused the cell cycle arrest in G1 phase, induced apoptosis in a concentration-dependent manner, significantly reduced mitochondrial membrane potential, increased intracellular ROS and Ca²⁺ levels, up-regulated the expression of Bax, cleaved caspase-9, cleaved caspase-3, and down-regulated the expression of Bcl-2 protein. A series of analyses confirmed that 12h can inhibit HCT-116 cells migration and induce apoptosis by a mechanism of the mitochondria-mediated pathway in the HCT-116 cell line. The present work indicates that compound 12h may merit further investigation as a potential therapeutic agent for colorectal cancer.

许多青蒿素衍生物对恶性肿瘤具有良好的抑制作用。在这项工作中，设计并合成了一系列含有哌嗪和氟基团的新型青蒿素衍生物，并通过¹ H-NMR、¹³ C-NMR 和 HRMS 技术对其结构进行了确认。评估了对各种癌细胞系的体外细胞毒性。在这些衍生物中，发现化合物12h不仅对 HCT-116 细胞表现出最好的活性（IC ₅₀ = 0.12± 0.05μM），而且对正常细胞系 L02 的毒性也很低（IC ₅₀ = 12.46±0.10 μM）。机制研究表明，化合物12h导致细胞周期停滞在 G1 期，以浓度依赖性方式诱导细胞凋亡，显着降低线粒体膜电位，增加细胞内 ROS 和 Ca ²⁺水平，上调 Bax、cleaved caspase-9、cleaved caspase-3 的表达，并下调 Bcl-2 蛋白的表达。一系列分析证实，12h可以通过 HCT-116 细胞系中线粒体介导的途径的机制抑制 HCT-116 细胞迁移并诱导细胞凋亡。目前的工作表明，化合物12h作为结直肠癌的潜在治疗剂可能值得进一步研究。