化学
细胞凋亡
药物重新定位
药品
IC50型
PI3K/AKT/mTOR通路
程序性细胞死亡
重新调整用途
细胞周期检查点
癌细胞
药理学
细胞周期
细胞生长
癌症
体外
医学
生物化学
生物
内科学
生态学
作者
Chao Mu,Rui-Kun Peng,Chunling Guo,Ao Li,Xiu-Ming Yang,Rong Zeng,Yulong Li,Jie Gu,Qin Ouyang
标识
DOI:10.1016/j.bmcl.2021.127997
摘要
Resistance phenomena during chemotherapy of tumor has been severely hampering the applications of chemotherapeutics. Due to advantage of drug repurposing, discovery of new chemosensitizers based on approved drugs is an effect strategy to find new candidates. Herein, we found antidepressant drug – sertraline, could sensitize drug-resistant gastric cancer cell (SGC-7901/DDP) with the IC50 value of 18.73 μM. To understand the structure–activity relationship and improve the activity, 30 derivatives were synthesized and evaluated. The IC50 value of the best compound was improved to 5.2 μM. Moreover, we found apoptosis induction and cell cycle arrest was the reason for the cell death of the drug-resistant cells after treatment of sertraline and derivatives, and PI3K/Akt/mTOR pathway was involved.
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