线粒体靶向6-(4-(二甲氨基)吡啶)甲基香豆素的合成及其辐射增敏作用

通过溴化和亲电两步反应得到线粒体靶向的抗肿瘤及辐射增敏药物6-(4-(二甲氨基)吡啶)甲基香豆素,探讨其对肺癌细胞系A549的抑制作用及辐射增敏作用。采用MTT法检测其对A549细胞的抑制率;克隆形成法检测辐射增敏作用(通过多靶单击方程拟合A549细胞的吸收剂量存活曲线,求出辐射增敏比,评价增敏效果);DCFH-DA法测定活性氧(Reactive oxygen species,ROS)含量。结果表明:A549细胞抑制率与药物浓度基本呈正相关;和照射组相比,联合组(照射加给药)存活分数明显降低(p0.05),辐射增敏比RSE=1.585;各剂量下,联合组与照射组相比,ROS均有显著性提高(p0.05)。结果提示,6-(4-(二甲氨基)吡啶)甲基香豆素对A549细胞具有抑制作用,且呈剂量依赖性;对A549细胞具有辐射增敏作用;可以显著提高A549细胞中的ROS含量。

Syntheses and radiosensitization effect of mitochondria-targeted 6-(4-(dimethylamine) pyridine) methyl coumarin

6-(4-(dimethylamine) pyridine) methyl coumarin with antitumor and radio sensitizing effect on A549 cells was synthesized through brominating and electrophonic reactions. The inhibition rate for A549 cells, the radio sensitizing effect, and the reactive oxygen species (ROS) volume were measured by MTT assay, clone formation assay (radio sensitizing effect (RSE) was calculated by the multitarget single hit model) and DCFH-DA method, respectively. The results showed that the inhibition rate for A549 cells was positive related to the drug concentration, and the survival fraction of combination group (radiation plus administration drug group) decreased significantly compared with radiation group (p<0.05),RSE=1.585, the ROS volume of combination group increased significantly compared with radiation group (p<0.05) under various doses. The results indicate that 6-(4-(dimethylamine) pyridine) methyl coumarin can inhibit A549 cells and the inhibition effect increase with the drug dose, and has radio sensitizing effect on A549 cells, and can increase the ROS volume in A549 cells significantly.