Design and Synthesis of 1,4‐Diformyl‐Piperazine Ferrostatin‐1 Derivatives as Novel Ferroptosis Inhibitors DOI Open Access
Yifan Zhang, Wei Guo, Hui Zheng

et al.

Chemical Biology & Drug Design, Journal Year: 2024, Volume and Issue: 104(5)

Published: Oct. 28, 2024

ABSTRACT The present study focuses on the design and synthesis of novel 1,4‐diformyl‐piperazine‐based ferrostatin‐1 (Fer‐1) derivatives, their evaluation against ferroptosis activity. synthesized compounds demonstrated significant anti‐ferroptosis activity in human umbilical vascular endothelial cells (HUVECs), with Compound 24 showing highest potency. Mechanistic studies revealed that effectively reduced intracellular reactive oxygen species (ROS) levels, mitigated mitochondrial damage, enhanced glutathione peroxidase 4 (GPX4) expression. Additionally, exhibited improved solubility plasma stability compared to control compounds, Fer‐1 JHL‐12. These findings suggest derivatives hold promise as therapeutic agents for ferroptosis‐associated cardiovascular diseases.

Language: Английский

Impairment of Endogenous H2S Pathway due to Aging and Endothelium Denudation in Mouse Isolated Thoracic Aorta DOI Creative Commons

Fatma Aydinoglu,

Eda Erdem,

Tuğba Toyran

et al.

Physiological Research, Journal Year: 2025, Volume and Issue: 1/2025, P. 59 - 68

Published: March 10, 2025

Hydrogen sulfide (H2S) is a gas neurotransmitter that synthesized in various mammalian tissues including vascular and regulates tone. The aim of this study to investigate whether the endogenous L-cysteine/H2S pathway impaired due aging endothelial denudation mouse isolated thoracic aorta. For purpose, young (3-4 months) old (23-25 mice were used experiments. effects endothelium on exogenous H2S-induced vasorelaxation investigated by cumulative L-cysteine-(1 µM-10 mM) NaHS-(1 µM-3 induced vasorelaxations, respectively. L-cysteine-induced relaxations reduced aorta compared mice. Also, vasorelaxant responses L-cysteine (1 rings with denuded-endothelium However, relaxation NaHS not altered age or denudation. loss staining CSE layer was observed Ach-induced (1-30 µM) almost abolished endothelium-denuded from both group. Ach intact tissue In conclusion, but decreased protein expression consistent decrease H2S concentration damage, suggesting may be lead enzyme signaling system damage

Language: Английский

Citations

0
Hydrogen sulfide preserves the function of senescent endothelium through SIRT2 mediated inflammatory inhibition DOI
Xiaoting Qin, Fan Lü,

Jie Wan

et al.

Journal of Molecular and Cellular Cardiology, Journal Year: 2025, Volume and Issue: unknown

Published: April 1, 2025

Language: Английский

Citations

0
BMSC-derived exosome overexpressing GATA-4 suppresses H/R-induced cardiomyocyte ferroptosis through miR-330-3p/BAP1/SLC7A11/IP3R axis and mPTP opening DOI Creative Commons
Zhiyuan Xiao,

Si Li,

Xinxin Wu

et al.

iScience, Journal Year: 2024, Volume and Issue: 27(10), P. 110784 - 110784

Published: Aug. 23, 2024

Language: Английский

Citations

2
Design and Synthesis of 1,4‐Diformyl‐Piperazine Ferrostatin‐1 Derivatives as Novel Ferroptosis Inhibitors DOI Open Access
Yifan Zhang, Wei Guo, Hui Zheng

et al.

Chemical Biology & Drug Design, Journal Year: 2024, Volume and Issue: 104(5)

Published: Oct. 28, 2024

ABSTRACT The present study focuses on the design and synthesis of novel 1,4‐diformyl‐piperazine‐based ferrostatin‐1 (Fer‐1) derivatives, their evaluation against ferroptosis activity. synthesized compounds demonstrated significant anti‐ferroptosis activity in human umbilical vascular endothelial cells (HUVECs), with Compound 24 showing highest potency. Mechanistic studies revealed that effectively reduced intracellular reactive oxygen species (ROS) levels, mitigated mitochondrial damage, enhanced glutathione peroxidase 4 (GPX4) expression. Additionally, exhibited improved solubility plasma stability compared to control compounds, Fer‐1 JHL‐12. These findings suggest derivatives hold promise as therapeutic agents for ferroptosis‐associated cardiovascular diseases.

Language: Английский

Citations

0