【摘 要】
：
本课题组的前期工作[1-2]表明含有长碳链的大黄素季铵盐在体内和体外都具有良好的抗癌活性.在此基础上,本文进行了如下工作.(1)继续对大黄素长碳链季铵盐的烃基结构进行优化,筛选得到了图1所示大黄素衍生物1,其抗癌活性(1.75μM,24h)和选择性均优于本课题组前期报道过的大黄素单季铵盐衍生物；(2)合成了2类大黄素双季铵盐衍生物,结构如图1中2和3所示,但它们的活性均没有超过1,原因可能是大黄素
【机 构】
：
福州大学化学化工学院 福州 350108
【出 处】
：
全国药物化学学术会议暨第四届中英药物化学学术会议
论文部分内容阅读
本课题组的前期工作[1-2]表明含有长碳链的大黄素季铵盐在体内和体外都具有良好的抗癌活性.在此基础上,本文进行了如下工作.(1)继续对大黄素长碳链季铵盐的烃基结构进行优化,筛选得到了图1所示大黄素衍生物1,其抗癌活性(1.75μM,24h)和选择性均优于本课题组前期报道过的大黄素单季铵盐衍生物；(2)合成了2类大黄素双季铵盐衍生物,结构如图1中2和3所示,但它们的活性均没有超过1,原因可能是大黄素双季铵盐的分子量普遍较大(1000左右)；(3)合成了大黄素单季鏻盐4 和双季鏻盐5,前者具有较高的抗癌活性(0.3-0.5μM,72h)；(4)合成了21个芦荟大黄素长碳链季铵盐6,其抗癌活性及构效关系均与大黄素季铵盐相似；(4)选择化合物1A进行了抗癌机制研究,发现大黄素季铵盐能降低癌细胞的跨膜电位和抗凋亡蛋白Bcl-2的表达,并增加其ROS产生能力且ROS产生能力与抗癌活性呈现正相关.
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