Identification of Boronic Acid Derivatives as an Active Form of N-Alkylaminoferrocene-Based Anticancer Prodrugs and Their Radiolabeling with 18F

Beitrag in einer Fachzeitschrift
(Originalarbeit)


Details zur Publikation

Autorinnen und Autoren: Daum S, Toms J, Reshetnikov V, Özkan H, Hampel F, Maschauer S, Hakimioun AH, Beierlein F, Sellner L, Schmitt M, Prante O, Mokhir A
Zeitschrift: Bioconjugate Chemistry
Jahr der Veröffentlichung: 2019
Band: 30
Heftnummer: 4
Seitenbereich: 1077-1086
ISSN: 1043-1802


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 developed the
efficient synthetic protocol for radiolabeling the hydrolyzed NAAF-based
prodrugs by [18F]fluoroglucosylation under the conditions of
the copper(I)-catalyzed azide–alkyne 1,3-dipolar cycloaddition and used
this protocol to prepare one representative hydrolyzed NAAF-based
prodrug radiolabeled with 18F. Finally, we studied the stability of the 18F-labeled compound in human serum in vitro and in rat blood in vivo and obtained preliminary data on its biodistribution in vivo
in mice carrying pancreatic (AR42J) and prostate (PC3) tumors by
applying PET imaging studies. The compound described in this paper will
help to understand in vivo effects (e.g., pharmacokinetics,
accumulation in organs, the nature of side effects) of these prodrugs
that will strongly contribute to their advancement to clinical trials.


FAU-Autorinnen und Autoren / FAU-Herausgeberinnen und Herausgeber

Beierlein, Frank Dr.
Computer-Chemie-Centrum
Daum, Steffen
Lehrstuhl für Organische Chemie II
Hakimioun, Amir Hossein
Computer-Chemie-Centrum
Hampel, Frank Dr.
Lehrstuhl für Organische Chemie I
Maschauer, Simone PD Dr.
Nuklearmedizinische Klinik
Mokhir, Andriy Prof. Dr.
Professur für Organische Chemie
Özkan, Hülya
Professur für Organische Chemie
Prante, Olaf Prof. Dr.
Professur für Molekulare Bildgebung und Radiochemie
Reshetnikov, Viktor
Professur für Organische Chemie
Toms, Johannes
Nuklearmedizinische Klinik


Einrichtungen weiterer Autorinnen und Autoren

Universitätsklinikum Heidelberg


Zitierweisen

APA:
Daum, S., Toms, J., Reshetnikov, V., Özkan, H., Hampel, F., Maschauer, S.,... Mokhir, A. (2019). Identification of Boronic Acid Derivatives as an Active Form of N-Alkylaminoferrocene-Based Anticancer Prodrugs and Their Radiolabeling with 18F. Bioconjugate Chemistry, 30(4), 1077-1086. https://dx.doi.org/10.1021/acs.bioconjchem.9b00019

MLA:
Daum, Steffen, et al. "Identification of Boronic Acid Derivatives as an Active Form of N-Alkylaminoferrocene-Based Anticancer Prodrugs and Their Radiolabeling with 18F." Bioconjugate Chemistry 30.4 (2019): 1077-1086.

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Zuletzt aktualisiert 2019-29-04 um 15:45