1. Identification of Boronic Acid Derivatives as an Active Form of N-Alkylaminoferrocene-Based Anticancer Prodrugs and Their Radiolabeling with 18F
- Author
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Steffen Daum, Leopold Sellner, Hülya Gizem Özkan, Andriy Mokhir, Simone Maschauer, Olaf Prante, Frank R. Beierlein, Viktor Reshetnikov, Frank Hampel, Johannes Toms, Michael Schmitt, and Amir Hossein Hakimioun
- Subjects
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 - Abstract
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...
- Published
- 2019
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