Identification of Boronic Acid Derivatives as an Active Form of N-Alkylaminoferrocene-Based Anticancer Prodrugs and Their Radiolabeling with 18F
| Autor: | Steffen Daum, Leopold Sellner, Hülya Gizem Özkan, Andriy Mokhir, Simone Maschauer, Olaf Prante, Frank R. Beierlein, Viktor Reshetnikov, Frank Hampel, Johannes Toms, Michael Schmitt, Amir Hossein Hakimioun |
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| Rok vydání: | 2019 |
| Předmět: |
Biomedical Engineering
Pharmaceutical Science Bioengineering 02 engineering and technology medicine.disease_cause 01 natural sciences Hydrolysis chemistry.chemical_compound In vivo medicine Pharmacology chemistry.chemical_classification Reactive oxygen species 010405 organic chemistry Organic Chemistry Prodrug 021001 nanoscience & nanotechnology Combinatorial chemistry 0104 chemical sciences chemistry Cell culture Cancer cell 0210 nano-technology Oxidative stress Boronic acid Biotechnology |
| Zdroj: | Bioconjugate Chemistry. 30:1077-1086 |
| ISSN: | 1520-4812 1043-1802 |
| DOI: | 10.1021/acs.bioconjchem.9b00019 |
| Popis: | N-Alkylaminoferrocene (NAAF)-based prodrugs are activated in the presence of elevated amounts of reactive oxygen species (ROS), which corresponds to cancer specific conditions, with formation of NAAF and p-quinone methide. Both products act synergistically by increasing oxidative stress in cancer cells that causes their death. Though it has already been demonstrated that the best prodrugs of this type retain their antitumor activity in vivo, the effects were found to be substantially weaker than those observed in cell cultures. Moreover, the mechanistic studies of these compounds in vivo are missing. For clarification of these important questions, labeling of the prodrugs with radioactive moieties would be necessary. In this paper, we first observed that the representative NAAF-based prodrugs are hydrolyzed in dilute aqueous solutions to the corresponding arylboronic acids. We confirmed that these products are responsible for ROS amplification and anticancer properties of the parent prodrugs. Next, we dev... |
| Databáze: | OpenAIRE |
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