Feng Nianlin, Qiu Xuemei, Li Fulian, Zhou Yue, Li Chengpeng, Liu Bingqian, Meng Jiao, Bai Song, Li Zhurui, Chen Danping, Wang Zhenchao
Guizhou Engineering Laboratory for Synthetic Drugs, College of Pharmacy, Guizhou University, Guiyang, 550025, China.
Guizhou Industry Polytechnic College, Guiyang, 550008, China.
Mol Divers. 2024 Dec 10. doi: 10.1007/s11030-024-11021-5.
Piperlongumine, a natural product from traditional Chinese medicine, shows promising antitumor effects but suffers from high toxicity. In this study, X and Q series Piperlongumine derivatives containing 1, 2, 3-triazole were designed and synthesized using the principle of molecular hybridization. The antitumor activity of these target compounds was evaluated, revealing significant activity compared to piperlongumine across four cancer cell lines. The structure-activity relationship of these compounds was analyzed using 3D-QSAR. Among these derivatives, compound 6Q demonstrated the highest antitumor activity against human chronic myeloid leukemia (K562) cells, with an IC value of 0.31 μM, low toxicity to normal cells, and a selectivity index (SI) of 11.2. Further in vitro experiments confirmed that 6Q induced apoptosis in K562 cells by disrupting mitochondrial membrane potential, activating the MAPK signaling pathway, and causing cell cycle arrest in the G2/M phase. These findings underscored the potential of the natural product derivative 6Q as a promising candidate for further development in cancer therapy.
胡椒碱是一种来自中药的天然产物，具有良好的抗肿瘤作用，但毒性较高。在本研究中，利用分子杂交原理设计并合成了含1,2,3-三唑的X和Q系列胡椒碱衍生物。对这些目标化合物的抗肿瘤活性进行了评估，结果显示与胡椒碱相比，它们在四种癌细胞系中均具有显著活性。使用3D-QSAR分析了这些化合物的构效关系。在这些衍生物中，化合物6Q对人慢性髓性白血病（K562）细胞表现出最高的抗肿瘤活性，IC值为0.31 μM，对正常细胞毒性低，选择性指数（SI）为11.2。进一步的体外实验证实，6Q通过破坏线粒体膜电位、激活MAPK信号通路并导致细胞周期阻滞在G2/M期，诱导K562细胞凋亡。这些发现强调了天然产物衍生物6Q作为癌症治疗进一步开发的有前景候选物的潜力。
