DMXAA-吡喃氧杂蒽酮杂化物增强了对具有多靶点功能的人类癌细胞的抑制活性。
DMXAA-pyranoxanthone hybrids enhance inhibition activities against human cancer cells with multi-target functions.
作者信息
Liu Jie, Zhou Fan, Zhang Lei, Wang Huailing, Zhang Jianrun, Zhang Cao, Jiang Zhenlei, Li Yanbing, Liu Zhijun, Chen Heru
机构信息
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, PR China.
出版信息
Eur J Med Chem. 2018 Jan 1;143:1768-1778. doi: 10.1016/j.ejmech.2017.10.074. Epub 2017 Oct 31.
Four 5,6-dimethylxanthone-4-acetic acid (D) and pyranoxanthone (P) hybrids (D-P-n) were design-synthesized based on multi-target-addressed strategy. D-P-4 was confirmed as the most active agent against HepG-2 cell line growth with an IC of 0.216 ± 0.031 μM. Apoptosis analysis indicated different contributions of early/late apoptosis/necrosis to cell death for both monomers, the combination (D + P in 1:1 mol ratio) and D-P-4. They all arrested more cells on S phase. Western Blot implied that D-P-4 regulated p53/MDM2 to a better healthy state. Moreover, it improved Bax/Bcl-2 signaling pathway to increase cancer cell apoptosis. In all cases studied, D-P-4 showed the best activity and synergistic effect. All the evidences support that D-P-4 is a better anti-cancer therapy with multi-target functions.
基于多靶点策略设计合成了四种5,6-二甲基呫吨酮-4-乙酸（D）和吡喃呫吨酮（P）的杂合物（D-P-n）。D-P-4被确认为对HepG-2细胞系生长最具活性的药物，其IC50为0.216±0.031μM。凋亡分析表明，早期/晚期凋亡/坏死对两种单体、组合体（D + P，摩尔比1:1）和D-P-4的细胞死亡有不同贡献。它们都使更多细胞停滞在S期。蛋白质免疫印迹表明，D-P-4将p53/MDM2调节至更好的健康状态。此外，它改善了Bax/Bcl-2信号通路以增加癌细胞凋亡。在所研究的所有情况下，D-P-4表现出最佳活性和协同效应。所有证据均支持D-P-4是一种具有多靶点功能的更好的抗癌疗法。
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