Fluoride-containing podophyllum derivatives exhibit antitumor activities through enhancing mitochondrial apoptosis pathway by increasing the expression of caspase-9 in HeLa cells.
Fluoride-containing podophyllum derivatives exhibit antitumor activities through enhancing mitochondrial apoptosis pathway by increasing the expression of caspase-9 in HeLa cells.
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含氟鬼臼衍生物通过增加 HeLa 细胞中 caspase-9 的表达来增强线粒体凋亡途径，从而表现出抗肿瘤活性
DOI：
10.1038/srep17175
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发表时间：
2015-11-26
影响因子：
4.6
通讯作者：
Tang YJ
中科院分区：
文献类型：
--
作者：
Zhao W;Yang Y;Zhang YX;Zhou C;Li HM;Tang YL;Liang XH;Chen T;Tang YJ
本工作旨在对含卤素苯胺类鬼药衍生物及其作用方式进行采样，并对氟、氯和溴进行深入比较，阐明氟取代对增强抗肿瘤活性的重要作用和影响，重点是抗肿瘤药物的药物合理设计。含氟苯胺鬼臼衍生物的肿瘤细胞毒性一般比含氯和含溴苯胺鬼臼衍生物提高10-100倍，因为氟化物不仅在质子溶剂中强溶剂化，而且在大多数非质子溶剂中形成紧密的离子对。与氯化物和溴化物相比，电负性较高的氟取代衍生物通过显著增加HeLa细胞中caspase-9的表达，显著增强了线粒体凋亡途径。目前的发现将刺激大量的研究，以开发基于鬼臼衍生物的新型先导化合物，特别是具有抗肿瘤活性的氟化物取代结构。
This work aims to provide sampling of halogen-containing aniline podophyllum derivatives and their mode of action with an in-depth comparison among fluorine, chloride and bromide for clarifying the important role and impact of fluorine substitution on enhancing antitumor activity, with an emphasis on the development of drug rational design for antitumor drug. The tumor cytotoxicity of fluoride-containing aniline podophyllum derivatives were in general improved by 10–100 times than those of the chloride and bromide-containing aniline podophyllum derivatives since fluoride could not only strongly solvated in protic solvents but also forms tight ion pairs in most aprotic solvents. When compared with chloride and bromide, the higher electronegativity fluoride substituted derivatives significantly enhanced mitochondrial apoptosis pathway by remarkably increasing the expression of caspase-9 in HeLa cells. The current findings would stimulate an enormous amount of research directed toward exploiting novel leading compounds based on podophyllum derivatives, especially for the fluoride-substituted structures with promising antitumor activity.