Guangzhou Health Center found that a class of bisbenzyl isoquinoline structural small molecules can be used as novel inhibitors of iron death

Recently, the team of Shu Xiaodong of the Guangzhou Institute of Biomedicine and Health, Chinese Academy of Sciences has identified a class of alkaloid small molecule compounds with a bisbenzyl isoquinoline (BBIQ) structure that can effectively inhibit ferrozois, and the related results are "Identification of a group of bisbenzylisoquinoline (BBIQ) compounds as ferroptosis inhibitors" Published in the journal Cell Death and Disease
.

Siderozois is a lipid peroxidation-induced programmed cell death that is involved in the pathogenesis of a variety of diseases, such as neurodegenerative diseases, ischemia-reperfusion injury, acute kidney injury, etc
.
Inhibiting the occurrence of ferrozois can effectively prevent the development of
related diseases.
At present, there is a lack of ferrozotic inhibitors that can be applied in clinical practice, so the development of effective small molecule inhibitors targeting other targets of the hemozotic pathway in vivo is an important topic
in related research fields.

Alkaloids are a class of nitrogen-containing natural compounds, which are present in a variety of Chinese herbal plants, most of which have good antioxidant activity
.
Since the occurrence of ferrozois involves redox processes, this study first identified a number of small molecule compounds that can effectively inhibit ferrozois by screening the library of alkaloids by cell model, and found that a class of alkaloids with BBIQ structure can effectively inhibit RSL3 or Erastin-induced ferrozois
through structural analysis.
Further biochemical analysis found that such small molecules inhibit iron death
mainly by scavenging lipid free radicals.
In high-dose folic acid-induced mouse acute kidney injury (AKI) models, many of the above small molecule inhibitors have good nephroprotective activity, so these BBIQ are a new class of small molecule inhibitors
of iron death with good in vivo activity.

Fan Yipu, a doctoral student in Shu Xiaodong's research group of Guangzhou Institute of Biomedicine and Health, and Yihan Zhang, an associate researcher at Guangzhou Laboratory of Regenerative Medicine and Health, are the co-first authors of the paper, Master Shi Kunyu of Guangzhou Laboratory of Regenerative Medicine and Health and Master Cheng Shan of Westlake University participated in the project, and Shu Xiaodong, researcher of Guangzhou Institute of Biomedicine and Health, is the corresponding author
of this paper.
The research has been supported
by a number of projects such as the National Key Research and Development Program, the Chinese Academy of Sciences Pilot Program, and the Guangzhou Science and Technology Program.

Paper link

Figure A: Cepharanthine clears lipid reactive oxygen species; Figure B: Cepharanthine inhibits AKI