Lysosome-targeting amplifiers of reactive oxygen species as anticancer prodrugs

Beitrag in einer Fachzeitschrift


Details zur Publikation

Autor(en): Daum S, Reshetnikov V, Sisa M, Dumych T, Lootsik MD, Bilyy R, Bila E, Janko C, Alexiou C, Herrmann M, Sellner L, Mokhir A
Zeitschrift: Angewandte Chemie (International ed. in English)
Jahr der Veröffentlichung: 2017
ISSN: 1521-3773


Abstract


Cancer cells produce elevated amounts of reactive oxygen species that has been used to design cancer specific prodrugs. Their activation relies on at least a bimolecular process, where a prodrug reacts with ROS. However, at low µM concentrations of the prodrugs and ROS the activation is usually inefficient. Herein we suggested and validated a potentially general approach for solving this intrinsic problem of ROS-dependent prodrugs. In particular, known 4-(N-ferrocenyl-N-benzylaminocarbonyloxymethyl)phenylboronic acid pinacol ester was converted to its lysosome specific analogue. Since lysosomes contain the higher concentration of active ROS than cytoplasm, activation of the latter prodrug was facilitated with respect to the parent compound. In particular, it was found to exhibit high anticancer activity in a variety of cancer cell lines (IC50 3.5-7.2 µM) and in vivo (40 mg/kg, NK/Ly murine model), but remained weakly toxic towards non-malignant cells (IC50 15-30 µM).



FAU-Autoren / FAU-Herausgeber

Alexiou, Christoph Prof. Dr.
Professur für Nanomedizin
Daum, Steffen
Lehrstuhl für Organische Chemie II
Herrmann, Martin Prof. Dr.
Medizinische Klinik 3 - Rheumatologie und Immunologie
Janko, Christina Dr. rer. nat.
Hals-Nasen-Ohren-Klinik - Kopf- und Halschirurgie
Mokhir, Andriy Prof. Dr.
Professur für Organische Chemie
Reshetnikov, Viktor
Lehrstuhl für Organische Chemie II
Sisa, Miroslav Dr.
Lehrstuhl für Organische Chemie II


Autor(en) der externen Einrichtung(en)
Danylo Halytsky Lviv National Medical University / Львiвський Національний Медичний Унiверситет iм. Данила Галицького
Universitätsklinikum Heidelberg


Zitierweisen

APA:
Daum, S., Reshetnikov, V., Sisa, M., Dumych, T., Lootsik, M.D., Bilyy, R.,... Mokhir, A. (2017). Lysosome-targeting amplifiers of reactive oxygen species as anticancer prodrugs. Angewandte Chemie (International ed. in English). https://dx.doi.org/10.1002/anie.201706585

MLA:
Daum, Steffen, et al. "Lysosome-targeting amplifiers of reactive oxygen species as anticancer prodrugs." Angewandte Chemie (International ed. in English) (2017).

BibTeX: 

Zuletzt aktualisiert 2018-05-10 um 02:14