2-羟基-1,4-萘醌衍生物诱导肺癌A549细胞凋亡的机制研究  

The mechanism of apoptosis induced by 2-hydroxy-1,4-naphthoquinone derivatives in lung cancer A549 cells

作　　者：赵俗 付毅红 李成朋 李洙锐 邵利辉 李焱[1] 陈丹萍 王贞超[1,2,3] 欧阳贵平 ZHAO Su;FU Yi-hong;LI Cheng-peng;LI Zhu-rui;SHAO Li-hui;LI Yan;CHEN Dan-ping;WANG Zhen-chao;OUYANG Gui-ping(School of Pharmaceutical Sciences,Guizhou University,Guiyang 550025,China;State Key Laboratory Breeding Base of Green Pesticide and Agricultural Bioengineering,Guizhou University,Guiyang 550025,China;Drug Synthetic Engineering Laboratory of Guizhou Province,Guiyang 550025,China)

机构地区：[1]贵州大学药学院,贵州贵阳550025 [2]贵州大学绿色农药与农业生物工程教育部重点实验室,贵州贵阳550025 [3]贵州省合成药物工程实验室,贵州贵阳550025

出　　处：《化学研究与应用》2023年第8期1870-1878,共9页Chemical Research and Application

基　　金：贵州省科技基础研究计划项目(ZK[2021]049)资助;贵州省普通高等学校青年科技人才成长项目(KY[2022]145)资助;贵州大学引进人才科研项目(贵大人基合字[2020]6号)资助;贵州大学培育项目(贵大培育[2019]48号)资助;国家自然科学基金项目(22007022)资助;贵州省自然科学基金项目(ZZK[2021]034)资助;贵州省教育厅青年科技人才成长项目(Qjh KY Zi[2021]041)资助。

摘　　要：本文设计合成了一系列2-羟基-1,4-萘醌衍生物,所有化合物均经过^(1)H-NMR、^(13)C-NMR、HRMS进行结构确认,通过细胞增殖实验筛选得到化合物5d对A549细胞表现出较高的抗肿瘤活性,IC_(50)值为4.91μmol·L^(-1),进一步通过细胞周期实验、蛋白质免疫印迹技术、分子对接等方法,研究了化合物5d诱导A549细胞凋亡的机制。结果发现,5d可以破坏线粒体膜功能、升高活性氧水平,并通过下调Akt和p-STAT3蛋白表达水平促进A549细胞的凋亡,具有潜在的药物开发及应用价值。In this paper,a series of 2-hydroxy-1,4-naphthoquinone derivatives were designed and synthesized,and compounds’structures were identified by^(1)H-NMR,^(13)C-NMR and HRMS.High antitumor activity of 5d against lung cancer A549 cells was observed with the IC_(50)as low as 4.91μmol·L^(-1).Further investigation of the mechanism in A549 cells was conducted via cell cycle assay,western blotting and molecular docking.The results showed that 5d could damage the mitochondrial functions,increase ROS levels,cause the downregulation of Akt and p-STAT3 proteins on the expression and arrest the cell cycle at the G2/M stages,which indicated that 5d induced lung cancer A549 cells apoptosis by Akt/STAT3 pathway and had potential application in the research and development of antitumor drugs.

关 键 词：1 4-萘醌衍生物 细胞凋亡 肺癌 AKT STAT3 

分 类 号：O625.462[理学—有机化学]