| RRC ID |
89957
|
| Author |
Homma T, Araki R, Nishimura Y, Ando N, Ie Y, Lin B, Nunomura K, Haruta J, Matsunaga S, Arisawa M, Tomita S.
|
| Title |
Polycyclic quinone compounds containing a six-membered silacycle suppress ferroptosis in vitro.
|
| Journal |
Free Radic Res
|
| Abstract |
Ferroptosis is a regulated form of cell death implicated in a wide range of pathological conditions. Iron-dependent lipid peroxidation driven by reactive oxygen species is a central feature. Because ferroptosis contributes to oxidative stress-induced tissue injury, including ischemia-reperfusion damage and neurodegenerative disorders, the suppression of this process has attracted considerable interest. Through a phenotypic screen of a unique chemical compound library from the University of Osaka, we identified a series of polycyclic quinone compounds containing a six-membered silacycle that exhibited protective effects against ferroptosis in vitro. These compounds selectively suppressed ferroptosis induced by various distinct ferroptosis inducers, while showing no protective effects against apoptosis. The ferroptosis-suppressive effects of these compounds were associated with reduced lipid peroxidation and decreased accumulation of ferrous iron in the mitochondria. Direct comparison with a carbon-substituted analog revealed that silicon substitution within the polycyclic quinone scaffold markedly enhanced the ferroptosis-suppressive activity. These results indicate that silicon-containing polycyclic quinone compounds represent a selective class of ferroptosis inhibitors and that silicon substitution confers a functional advantage for ferroptosis suppression.
|
| Volume |
60(4)
|
| Pages |
427-439
|
| Published |
2026-1-1
|
| DOI |
10.1080/10715762.2026.2678405
|
| PMID |
42210651
|
| MeSH |
Animals
Ferroptosis* / drug effects
Humans
Lipid Peroxidation / drug effects
Polycyclic Compounds* / chemistry
Polycyclic Compounds* / pharmacology
Quinones* / chemistry
Quinones* / pharmacology
Reactive Oxygen Species / metabolism
|
| Resource |
| Human and Animal Cells |
HL-60 |
