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 |
|
| | | Lehrstuhl für Organische Chemie II |
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| Herrmann, Martin Prof. Dr. |
| | Medizinische Klinik 3 - Rheumatologie und Immunologie |
|
| Janko, Christina Dr. rer. nat. |
| | Hals-Nasen-Ohren-Klinik - Kopf- und Halschirurgie |
|
| | | Professur für Organische Chemie |
|
| | | Lehrstuhl für Organische Chemie II |
|
| | | 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). |