| 论文编号: |
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| 第一作者所在部门: |
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| 中文论文题目: |
Identification of a group of bisbenzylisoquinoline (BBIQ) compounds as ferroptosis inhibitors |
| 英文论文题目: |
Identification of a group of bisbenzylisoquinoline (BBIQ) compounds as ferroptosis inhibitors |
| 作者: |
Yipu Fan, Yihan Zhang, Kunyu Shi, Shan Cheng, Duanqing Pei and Xiaodong Shu |
| 论文出处: |
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| 刊物名称: |
Cell Death＆Disease |
| 年: |
2022 |
| 卷: |
13 |
| 期: |
11 |
| 页: |
1000 |
| 联系作者: |
Xiaodong Shu |
| 收录类别: |
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| 影响因子: |
9.696 |
| 摘要: |
Ferroptosis induced by detrimental accumulation of lipid peroxides has been recently linked to a variety of pathological conditions ranging from acute tissue injuries to chronic degenerative diseases and suppression of ferroptosis by small chemical inhibitors is beneficial to the prevention and treatment of these diseases. However, in vivo applicable small chemical ferroptosis inhibitors are limited currently. In this study, we screened an alkaloid natural compound library for compounds that can inhibit RSL3-induced ferroptosis in HT1080 cells and identified a group of bisbenzylisoquinoline (BBIQ) compounds as novel ferroptosis-specific inhibitors. These BBIQ compounds are structurally different from known ferroptosis inhibitors and they do not appear to regulate iron homeostasis or lipid ROS generation pathways, while they are able to scavenge 1,1-diphenyl-2-picryl-hydrazyl (DPPH) in cell-free reactions and prevent accumulation of lipid peroxides in living cells. These BBIQ compounds demonstrate good in vivo activities as they effectively protect mice from folic acid-induced renal tubular ferroptosis and acute kidney injury. Several BBIQ compounds are approved drugs in Japan and China for traditional uses and cepharanthine is currently in clinical trials against SARS-CoV-2, our discovery of BBIQs as in vivo applicable ferroptosis inhibitors will expand their usage to prevent ferroptotic tissue damages under various pathological conditions. |
| 英文摘要: |
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