Liu Jie, Zhang Jianrun, Wang Huailing, Liu Zhijun, Zhang Cao, Jiang Zhenlei, Chen Heru
Institute of Traditional Chinese Medicine and Natural Products, College of Pharmacy, Jinan University, Guangzhou 510632, PR China.
School of Food Sciences and Engineering, South China University of Technology, Guangzhou 510641, China.
Eur J Med Chem. 2017 Jun 16;133:50-61. doi: 10.1016/j.ejmech.2017.03.068. Epub 2017 Mar 29.
34 Xanthones were synthesized by microwave assisted technique. Their in vitro inhibition activities against five cell lines growth were evaluated. The SAR has been thoroughly discussed. 7-Bromo-1,3-dihydroxy-9H-xanthen-9-one (3-1) was confirmed as the most active agent against MDA-MB-231 cell line growth with an IC of 0.46 ± 0.03 μM. Combination of 3-1 and 5,6-dimethylxanthone-4-acetic acid (DMXAA) showed the best synergistic effect. Apoptosis analysis indicated different contributions of early/late apoptosis and necrosis to cell death for both monomers and the combination. Western Blot implied that the combination regulated p53/MDM2 to a better healthy state. Furthermore, 3-1 and DMXAA arrested more cells on G2/M phase; while the combination arrested more cells on S phase. All the evidences support that the 3-1/DMXAA combination is a better anti-cancer therapy.
通过微波辅助技术合成了34种呫吨酮。评估了它们对五种细胞系生长的体外抑制活性。对构效关系进行了深入讨论。7-溴-1,3-二羟基-9H-呫吨-9-酮（3-1）被确认为对MDA-MB-231细胞系生长最具活性的药物，其半数抑制浓度为0.46±0.03μM。3-1与5,6-二甲基呫吨酮-4-乙酸（DMXAA）的组合显示出最佳的协同效应。凋亡分析表明，早期/晚期凋亡和坏死对单体及组合的细胞死亡有不同贡献。蛋白质免疫印迹法表明，该组合将p53/MDM2调节至更好的健康状态。此外，3-1和DMXAA使更多细胞停滞在G2/M期；而组合使更多细胞停滞在S期。所有证据均支持3-1/DMXAA组合是一种更好的抗癌疗法。
