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]Laboratory of Lung Cancer, Lung Cancer Center, 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]Department of Cardiovascular Surgery, West China Hospital, Sichuan University, Chengdu 610041, China.四川大学华西医院
A series of novel naphthoquinone-furan-2-cyanoacryloyl hybrids were designed; they were synthesized and preliminarily evaluated for their anti-proliferative activities in vitro against several cancer cell lines and normal cells. The most potent compound, 5c, inhibited the proliferation of HeLa cells (IC50 value of 3.10 ± 0.02 μM) and colony survival, and it induced apoptosis while having relatively weaker effects on normal cells. Compound 5c also triggered ROS generation and accumulation, thus partially contributing to the observed cell apoptosis. A Western blotting analysis demonstrated that compound 5c inhibited the phosphorylation of STAT3. Furthermore, a biolayer interferometry (BLI) analysis confirmed that compound 5c had a direct effect on STAT3, with a KD value of 13.0 μM. Molecular docking showed that 5c specifically occupied the subpockets in the SH2 domain, thereby blocking the whole transmission signaling process. Overall, this study provides an important structural reference for the development of effective antitumor agents.
基金：
National Natural Science Foundation of China (Grant
No. 21977076) and 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.[4]State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, Chengdu 610041, China.
推荐引用方式(GB/T 7714)：
Liu Pingxian,Fan Dongmei,Qiao Wenliang,et al.SAR Study and Molecular Mechanism Investigation of Novel Naphthoquinone-furan-2-cyanoacryloyl Hybrids with Antitumor Activity[J].Pharmaceutics.2022,14(10):doi:10.3390/pharmaceutics14102104.
APA：
Liu Pingxian,Fan Dongmei,Qiao Wenliang,He Xinlian,Zhang Lidan...&Yang Tao.(2022).SAR Study and Molecular Mechanism Investigation of Novel Naphthoquinone-furan-2-cyanoacryloyl Hybrids with Antitumor Activity.Pharmaceutics,14,(10)
MLA：
Liu Pingxian,et al."SAR Study and Molecular Mechanism Investigation of Novel Naphthoquinone-furan-2-cyanoacryloyl Hybrids with Antitumor Activity".Pharmaceutics 14..10(2022)
