Cyclic vinyl sulfones activate NRF2 to protect from oxidative stress-induced programmed necrosis

Standard

Cyclic vinyl sulfones activate NRF2 to protect from oxidative stress-induced programmed necrosis. / Davidovich, Pavel; Nikolaev, Dmitriy; Khadiullina, Raniya; Gurzhiy, Vladislav; Bulatov, Emil.

в: Bioorganic and Medicinal Chemistry Letters, Том 117, 130058, 01.03.2025.

Результаты исследований: Научные публикации в периодических изданиях › статья › Рецензирование

Author

Davidovich, Pavel ; Nikolaev, Dmitriy ; Khadiullina, Raniya ; Gurzhiy, Vladislav ; Bulatov, Emil. / Cyclic vinyl sulfones activate NRF2 to protect from oxidative stress-induced programmed necrosis. в: Bioorganic and Medicinal Chemistry Letters. 2025 ; Том 117.

BibTeX

@article{fc9bf458009c4ef28192a7cfb721fc57,

title = "Cyclic vinyl sulfones activate NRF2 to protect from oxidative stress-induced programmed necrosis",

abstract = "The NRF2 transcriptional factor is a member of cellular stress response machinery and is activated in response to oxidative stress caused either by cellular homeostasis imbalance or by environmental challenges. NRF2 levels are stringently controlled by rapid and continuous proteasomal degradation. KEAP1 is a specific NRF2 binding protein that acts as a bridge between NRF2 and the E3 ligase Cullin-3. In this study, we examine model cyclic vinyl sulfone derivatives as potential NRF2 activating probes. Previously, we and other authors have found anti-inflammatory properties of these compounds in in vivo models; however, the mechanism of action remained unknown. Here, we show that the naphthohydroquinone derivative LCB1353 efficiently stabilizes NRF2 protein levels and upregulates its target genes. At low 5-10 µM concentrations LCB1353 protects non-small cell lung cancer H1299 cells from ferroptotic death induced by cytotoxic concentrations of RSL3, reducing cell death from 90 % to 5 %. Thus, we suggest that cyclic vinyl sulfones are promising scaffolds for the design of protective molecules for conditions associated with toxic and inflammatory levels of oxidative stress.",

keywords = "Cell death, Cyclic vinyl sulfones, Ferroptosis, NRF2, Programmed necrosis, Protection",

author = "Pavel Davidovich and Dmitriy Nikolaev and Raniya Khadiullina and Vladislav Gurzhiy and Emil Bulatov",

year = "2025",

month = mar,

day = "1",

doi = "10.1016/j.bmcl.2024.130058",

language = "English",

volume = "117",

journal = "Bioorganic and Medicinal Chemistry Letters",

issn = "0960-894X",

publisher = "Elsevier",

}

RIS

TY - JOUR

T1 - Cyclic vinyl sulfones activate NRF2 to protect from oxidative stress-induced programmed necrosis

AU - Davidovich, Pavel

AU - Nikolaev, Dmitriy

AU - Khadiullina, Raniya

AU - Gurzhiy, Vladislav

AU - Bulatov, Emil

PY - 2025/3/1

Y1 - 2025/3/1

N2 - The NRF2 transcriptional factor is a member of cellular stress response machinery and is activated in response to oxidative stress caused either by cellular homeostasis imbalance or by environmental challenges. NRF2 levels are stringently controlled by rapid and continuous proteasomal degradation. KEAP1 is a specific NRF2 binding protein that acts as a bridge between NRF2 and the E3 ligase Cullin-3. In this study, we examine model cyclic vinyl sulfone derivatives as potential NRF2 activating probes. Previously, we and other authors have found anti-inflammatory properties of these compounds in in vivo models; however, the mechanism of action remained unknown. Here, we show that the naphthohydroquinone derivative LCB1353 efficiently stabilizes NRF2 protein levels and upregulates its target genes. At low 5-10 µM concentrations LCB1353 protects non-small cell lung cancer H1299 cells from ferroptotic death induced by cytotoxic concentrations of RSL3, reducing cell death from 90 % to 5 %. Thus, we suggest that cyclic vinyl sulfones are promising scaffolds for the design of protective molecules for conditions associated with toxic and inflammatory levels of oxidative stress.

AB - The NRF2 transcriptional factor is a member of cellular stress response machinery and is activated in response to oxidative stress caused either by cellular homeostasis imbalance or by environmental challenges. NRF2 levels are stringently controlled by rapid and continuous proteasomal degradation. KEAP1 is a specific NRF2 binding protein that acts as a bridge between NRF2 and the E3 ligase Cullin-3. In this study, we examine model cyclic vinyl sulfone derivatives as potential NRF2 activating probes. Previously, we and other authors have found anti-inflammatory properties of these compounds in in vivo models; however, the mechanism of action remained unknown. Here, we show that the naphthohydroquinone derivative LCB1353 efficiently stabilizes NRF2 protein levels and upregulates its target genes. At low 5-10 µM concentrations LCB1353 protects non-small cell lung cancer H1299 cells from ferroptotic death induced by cytotoxic concentrations of RSL3, reducing cell death from 90 % to 5 %. Thus, we suggest that cyclic vinyl sulfones are promising scaffolds for the design of protective molecules for conditions associated with toxic and inflammatory levels of oxidative stress.

KW - Cell death

KW - Cyclic vinyl sulfones

KW - Ferroptosis

KW - NRF2

KW - Programmed necrosis

KW - Protection

UR - https://www.mendeley.com/catalogue/95aa73e4-172c-3ef1-9cca-e2be026c9e9b/

U2 - 10.1016/j.bmcl.2024.130058

DO - 10.1016/j.bmcl.2024.130058

M3 - Article

C2 - 39644937

VL - 117

JO - Bioorganic and Medicinal Chemistry Letters

JF - Bioorganic and Medicinal Chemistry Letters

SN - 0960-894X

M1 - 130058

ER -

ID: 128403703