机构：[1]Laboratory of Human Diseases and Immunotherapies, West China Hospital, Sichuan University, Chengdu 610041, China.四川大学华西医院[2]Institute of Immunology and Inflammation, Frontiers Science Center for Disease-Related Molecular Network, West China Hospital, Sichuan University, Chengdu 610041, China.四川大学华西医院[3]Department of Cardiovascular Surgery, West China Hospital, Sichuan University, Chengdu 610041, China.四川大学华西医院[4]State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, Chengdu 610041, China.四川大学华西医院[5]School of Food and Bioengineering, Xihua University, Chengdu 610041, China.
A novel class of quinoxaline-arylfuran derivatives were designed, synthesized, and preliminarily evaluated for their antiproliferative activities in vitro against several cancer cell lines and normal cells. The representative derivative QW12 exerts a potent antiproliferative effect against HeLa cells (IC50 value of 10.58 μM), through inducing apoptosis and triggering ROS generation and the accumulation of HeLa cells in vitro. Western blot analysis showed that QW12 inhibits STAT3 phosphorylation (Y705) in a dose-dependent manner. The BLI experiment directly demonstrated that QW12 binds to the STAT3 recombination protein with a KD value of 67.3 μM. Furthermore, molecular docking investigation showed that QW12 specifically occupies the pY+1 and pY-X subpocket of the SH2 domain, thus blocking the whole transmission signaling process. In general, these findings indicated that the study of new quinoxaline-aryfuran derivatives as inhibitors of STAT3 may lead to new therapeutic medical applications for cancer in the future.
基金：
National Natural Science Foundation of China (Grant NO.
21977076) and the 1·3·5 project for disciplines of excellence, West China Hospital, Sichuan University
(ZYJC18003).
语种：
外文
PubmedID：
中科院(CAS)分区：
出版当年[2022]版：
大类|2 区医学
小类|2 区药学
最新[2023]版：
大类|3 区医学
小类|2 区药学
第一作者：
第一作者机构：[1]Laboratory of Human Diseases and Immunotherapies, West China Hospital, Sichuan University, Chengdu 610041, China.[2]Institute of Immunology and Inflammation, Frontiers Science Center for Disease-Related Molecular Network, West China Hospital, Sichuan University, Chengdu 610041, China.
共同第一作者：
通讯作者：
通讯机构：[1]Laboratory of Human Diseases and Immunotherapies, West China Hospital, Sichuan University, Chengdu 610041, China.[2]Institute of Immunology and Inflammation, Frontiers Science Center for Disease-Related Molecular Network, West China Hospital, Sichuan University, Chengdu 610041, China.[3]Department of Cardiovascular Surgery, West China Hospital, Sichuan University, Chengdu 610041, China.
推荐引用方式(GB/T 7714)：
Fan Dongmei,Liu Pingxian,Jiang Yunhan,et al.Discovery and SAR Study of Quinoxaline-Arylfuran Derivatives as a New Class of Antitumor Agents[J].Pharmaceutics.2022,14(11):doi:10.3390/pharmaceutics14112420.
APA：
Fan Dongmei,Liu Pingxian,Jiang Yunhan,He Xinlian,Zhang Lidan...&Yang Tao.(2022).Discovery and SAR Study of Quinoxaline-Arylfuran Derivatives as a New Class of Antitumor Agents.Pharmaceutics,14,(11)
MLA：
Fan Dongmei,et al."Discovery and SAR Study of Quinoxaline-Arylfuran Derivatives as a New Class of Antitumor Agents".Pharmaceutics 14..11(2022)
