Optimizing Therapeutics for Intratumoral Cancer Treatments: Antiproliferative Vanadium Complexes in Glioblastoma

International Journal of Molecular Sciences, Journal Year: 2025, Volume and Issue: 26(3), P. 994 - 994

Published: Jan. 24, 2025

Glioblastoma, an aggressive cancer, is difficult to treat due its location, late detection, drug resistance, and poor absorption of chemotherapeutics. Intratumoral administration offers a promising potential treatment alternative with localized delivery minimal systemic toxicity. Vanadium(V) coordination complexes, incorporating Schiff base catecholate ligands, have shown effects as antiproliferative agents tunable efficacy reactivity, stability, steric bulk, hydrophobicity, uptake, toxicity optimized for the intratumoral vehicle. A new series oxovanadium(V) base–catecholate complexes were synthesized characterized using nuclear magnetic resonance (NMR), UV-Vis, infrared spectroscopy mass spectrometry. Stability under physiological conditions was assessed via UV-Vis spectroscopy, activity evaluated in T98G glioblastoma SVG p12 normal glial cells viability assays. The newly [VO(3-tBuHSHED)(TIPCAT)] complex more stable (t1/2 ~ 4.5 h) had strong (IC50 1.5 µM), comparing favorably current lead compound, [VO(HSHED)(DTB)]. structural modifications enhanced bulk through substitution iso-propyl tert-butyl groups. improved properties attributed hindrance associated catecholato well formation non-toxic byproducts upon degradation. emerges candidate therapy by demonstrating stability greater selectivity, which highlights role strategic ligand design developing therapies resistant cancers. In reporting class compounds effective against cells, we describe generally desirable that drugs being developed should have.

Language: Английский

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Hydrolysis, Ligand Exchange, and Redox Properties of Vanadium Compounds: Implications of Solution Transformation on Biological, Therapeutic, and Environmental Applications

Chemical Reviews, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 16, 2025

Vanadium is a transition metal with important industrial, technological, biological, and biomedical applications widespread in the environment living beings. The different reactions that vanadium compounds (VCs) undergo presence of proteins, nucleic acids, lipids metabolites under mild physiological conditions are reviewed. In present naturally or through anthropogenic sources, latter having an environmental impact caused by dispersion VCs atmosphere aquifers. has versatile chemistry interconvertible oxidation states, variable coordination number geometry, ability to form polyoxidovanadates various nuclearity structures. If VC added water-containing it can hydrolysis, ligand-exchange, redox, other types changes, determined speciation vanadium. Importantly, solution likely differ from introduced into system varies concentration. Here, hydrolytic ligand-exchange chemical reactions, influence pH, concentration, salt, specific solutes, biomolecules, on described. One our goals this work highlight need for assessment speciation, so beneficial toxic species might be identified mechanisms action elucidated.

Language: Английский

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Reactivity in cell culture medium and in vitro anticancer activity of 3,5-di-tert-butylcatechol: link to metal-catechol interactions

Frontiers in Chemical Biology, Journal Year: 2025, Volume and Issue: 4

Published: Feb. 3, 2025

Introduction Catechol moieties are common in natural bioactive molecules, and their ability to bind metal ions is widely explored both naturally with siderophores the development of metal-based drugs. The reactivities biology activities a sterically hindered model catechol compound, 3,5-di- tert -butylcatechol (dtbH 2 ) its oxidation product -butyl- o -quinone (dtbQ), were studied cell culture medium understand better medicinal roles this class molecules. Methods Anti-proliferative dtbH dtbQ fresh aged solutions molecules two human cancer lines, T98G (glioblastoma) A549 (lung carcinoma). Electrospray mass spectrometry UV/Vis spectroscopy used study buffer medium, presence absence glutathione imidazole. Results Discussion showed high anti-proliferative activity (IC 50 < 10 μM 72 h assays) lines added ions. was observed when freshly while pre-incubation for 24 reduced 5-10-fold. This deactivation avoided biological reductant, (GSH), at physiologically relevant intracellular concentration (5.0 mM). These results explained by speciation studies (UV/Vis spectrometry) aqueous buffers, or organic solvents GSH. that redox equilibrium established between dtbQ, latter rapidly coupling GSH an oxidative manner. resultant adduct likely be responsible toxicity GSH-rich cells via oxygen-dependent radical chain reactions. Deactivation due reactions nucleophiles, such as amino acids, followed formation polymeric species. reported V(V)-catecholato complexes can combination efficient cellular uptake rapid decomposition thiol-rich environment active V(V) /dtbQ adducts thiols (mainly GSH). Slower thiol-poor extracellular environments. data show crucial not only but also ligands dissociates.

Language: Английский

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Synthesis, crystal structure, computational and solution studies of a new phosphotetradecavanadate salt. Assessment of its effect on U87 glioblastoma cells

Journal of Inorganic Biochemistry, Journal Year: 2025, Volume and Issue: 269, P. 112882 - 112882

Published: March 9, 2025

Language: Английский

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Exploring polyoxidovanadate–protein interaction

Trends in Chemistry, Journal Year: 2024, Volume and Issue: unknown

Published: Dec. 1, 2024

Language: Английский

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