RRC ID 89957
著者 Homma T, Araki R, Nishimura Y, Ando N, Ie Y, Lin B, Nunomura K, Haruta J, Matsunaga S, Arisawa M, Tomita S.
タイトル Polycyclic quinone compounds containing a six-membered silacycle suppress ferroptosis in vitro.
ジャーナル 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.
巻・号 60(4)
ページ 427-439
公開日 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
リソース情報
ヒト・動物細胞 HL-60