Identifying eleven new ferroptosis inhibitors as neuroprotective agents from FDA-approved drugs.
Bioorg Chem
; 146: 107261, 2024 May.
Article
in En
| MEDLINE
| ID: mdl-38460336
ABSTRACT
With increasing evidence that ferroptosis is associated with diverse neurological disorders, targeting ferroptosis offers a promising avenue for developing effective pharmaceutical agents for neuroprotection. In this study, we identified ferroptosis inhibitors as neuroprotective agents from US Food and Drug Administration (FDA)-approved drugs. 1176 drugs have been screened against erastin-induced ferroptosis in HT22 cells, resulting in 89 ferroptosis inhibitors. Among them, 26 drugs showed significant activity with EC50 below10 µM. The most active ferroptosis inhibitor is lumateperone tosylate at nanomolar level. 11 drugs as ferroptosis inhibitors were not reported previously. Further mechanistic studies revealed that their mechanisms of actions involve free radical scavenging, Fe2+ chelation, and 15-lipoxygenase inhibition. Notably, the active properties of some drugs were firstly revealed here. These ferroptosis inhibitors increase the chemical diversity of ferroptosis inhibitors, and offer new therapeutic possibilities for the treatments of related neurological diseases.
Key words
Full text:
1
Database:
MEDLINE
Main subject:
Neuroprotective Agents
/
Ferroptosis
Limits:
Humans
Country/Region as subject:
America do norte
Language:
En
Year:
2024
Type:
Article