Chen Hao, Yang Xiao, Yu Zongmin, Cheng Ziying, Yuan Hu, Zhao Zeng, Wu Guozhen, Xie Ning, Yuan Xing, Sun Qingyan, Zhang Weidong
School of Pharmacy, Second Military Medical University, Shanghai 200433, China; State Key Laboratory of Innovative Natural Medicine and TCM Injections, Jiangxi Qingfeng Pharmaceutical Co., Ltd, Ganzhou 341000, Jiangxi, China.
School of Pharmacy, Second Military Medical University, Shanghai 200433, China.
Eur J Med Chem. 2018 Apr 10;149:90-97. doi: 10.1016/j.ejmech.2018.02.073. Epub 2018 Feb 23.
A series of α-santonin-derived compounds as potentially anti-hepatoma agents were designed and synthesized in an effort to find novel therapeutic agents. Among them, derivative 5h was more potent than the positive control 5-fluorouracil (5-Fu) on HepG-2, QGY-7703 and SMMC-7721 with IC values of 7.51, 3.06 and 4.08 μM, respectively. The structure-activity relationships (SARs) of these derivatives were discussed. In addition, flow cytometry and western blot assay revealed that the derivatives induced hepatoma cells apoptosis by facilitating apoptosis-related proteins expressions. Our findings suggested that these α-santonin-derived analogues hold promise as chemotherapeutic agents for the treatment of human hepatocellular cancer.
为了寻找新型治疗药物，设计并合成了一系列潜在的抗肝癌α-山道年衍生物。其中，衍生物5h在HepG-2、QGY-7703和SMMC-7721细胞上比阳性对照5-氟尿嘧啶（5-Fu）更具活性，IC值分别为7.51、3.06和4.08μM。讨论了这些衍生物的构效关系（SARs）。此外，流式细胞术和蛋白质印迹分析表明，这些衍生物通过促进凋亡相关蛋白的表达诱导肝癌细胞凋亡。我们的研究结果表明，这些α-山道年衍生物有望成为治疗人类肝细胞癌的化疗药物。
