Inhibition of Thioredoxin-Reductase by Auranofin as a Pro-Oxidant Anticancer Strategy for Glioblastoma: In Vitro and In Vivo Studies

International Journal of Molecular Sciences, Journal Year: 2025, Volume and Issue: 26(5), P. 2084 - 2084

Published: Feb. 27, 2025

Reactive oxygen species (ROS) play a key role in cancer progression and antitumor therapy. Glioblastoma is highly heterogeneous tumor with different cell populations exhibiting various redox statuses. Elevated ROS levels cells promote growth simultaneously make them more sensitive to anticancer drugs, but further elevation leads death apoptosis. Meanwhile, subsets of cells, such glioblastoma stem (GSC) or the microenvironment (TME), demonstrate adaptive mechanisms excessive production by developing effective antioxidant systems as glutathione- thioredoxin-dependent. GSCs higher chemoresistance lower than other glioma while TME create pro-oxidative environment have immunosuppressive effects. Both subpopulations become an attractive target for therapies. Increased expression thioredoxin reductase (TrxR) often associated poor patient survival. Various TrxR inhibitors been investigated potential therapies, including nitrosoureas, flavonoids metallic complexes. Gold derivatives are irreversible TrxR. Among them, auranofin (AF), selective inhibitor, has proven its effectiveness drug treatment rheumatoid arthritis efficacy agent demonstrated preclinical studies vitro vivo. However, clinical application AF could be challenging due low solubility insufficient delivery glioblastoma. Different strategies hydrophobic drugs used increase concentration brain. Combining therapeutic approaches that affect status new strategy treating brain diseases.

Language: Английский

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Functional utility of gold complexes with phosphorus donor ligands in biological systems

Coordination Chemistry Reviews, Journal Year: 2024, Volume and Issue: 522, P. 216208 - 216208

Published: Sept. 27, 2024

Language: Английский

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Structure, stability, and dynamics of inclusion complexes formed from auranofin derivatives and hydroxypropyl-β-cyclodextrin

Journal of Inclusion Phenomena and Macrocyclic Chemistry, Journal Year: 2024, Volume and Issue: 104(9-10), P. 513 - 526

Published: July 12, 2024

Language: Английский

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Structure, stability, and dynamics of the inclusion complexes formed by auranofin derivatives and hydroxypropyl-β-cyclodextrin

Research Square (Research Square), Journal Year: 2024, Volume and Issue: unknown

Published: June 14, 2024

The inclusion compounds of auranofin (AF) and its iodide derivative (AF-I) with HP-b-CD were recently identified characterized experimentally. In the present work, classical molecular dynamics quantum computational GFN2-xTB method applied to investigate processes. As a result, both approaches addressed AF-I@HP-β-CD as most favorable system, observed higher stability was explained by entropy solvation factors, providing constant (logK_1:1) in good agreement experiment: 0.21 – 1.21 for AF@HP-β-CD 1.31 2.33 (experimental values are 1.48 2.52, respectively). preferred mode has triethylphosphine (-PEt₃) group pointed toward head portion HP-β-CD where hydroxypropyl groups attached (labeled P2). P2 showed short contacts between -CH₂CH₃ -H3 only (inside CD cavity), which is also supported ROESY experiments.

Language: Английский

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Artemis and its role in cancer

Translational Oncology, Journal Year: 2024, Volume and Issue: 51, P. 102165 - 102165

Published: Nov. 8, 2024

Language: Английский

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Chitosan Nanoparticles: Drug Delivery Carriers in Cancer Therapy

Advances in polymer science, Journal Year: 2024, Volume and Issue: unknown

Published: Jan. 1, 2024

Language: Английский

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