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Lysosome-Targeting Amplifiers of Reactive Oxygen Species as Anticancer Prodrugs
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SYSNO ASEP 0485730 Document Type J - Journal Article R&D Document Type Journal Article Subsidiary J Článek ve WOS Title Lysosome-Targeting Amplifiers of Reactive Oxygen Species as Anticancer Prodrugs Author(s) Daum, S. (DE)
Reshetnikov, M.S.V. (DE)
Šíša, Miroslav (UEB-Q) ORCID
Dumych, T. (UA)
Lootsik, M. D. (UA)
Bilyy, R. (UA)
Bila, E. (UA)
Janko, C. (DE)
Alexiou, C. (DE)
Herrmann, M. (DE)
Sellner, L. (DE)
Mokhir, A. (DE)Number of authors 12 Source Title Angewandte Chemie - International Edition. - : Wiley - ISSN 1433-7851
Roč. 56, č. 49 (2017), s. 15545-15549Number of pages 5 s. Language eng - English Country DE - Germany Keywords aminoferrocene ; cancer ; lysosomes ; prodrugs ; reactive oxygen species Subject RIV ED - Physiology OECD category Organic chemistry Institutional support UEB-Q - RVO:61389030 UT WOS 000416244200006 EID SCOPUS 85033445233 DOI 10.1002/anie.201706585 Annotation Cancer cells produce elevated levels of reactive oxygen species, which has been used to design cancer specific prodrugs. Their activation relies on at least a bimolecular process, in which a prodrug reacts with ROS. However, at low micromolar concentrations of the prodrugs and ROS, the activation is usually inefficient. Herein, we propose and validate a potentially general approach for solving this intrinsic problem of ROS-dependent prodrugs. In particular, known prodrug 4-(N-ferrocenyl-N-benzylaminocarbonyloxymethyl)phenylboronic acid pinacol ester was converted into its lysosome-specific analogue. Since lysosomes contain a higher concentration of active ROS than the cytoplasm, activation of the prodrug was facilitated with respect to the parent compound. Moreover, it was found to exhibit high anticancer activity in a variety of cancer cell lines (IC 50 =3.5–7.2 μm) and in vivo (40 mg kg −1 , NK/Ly murine model) but remained weakly toxic towards non-malignant cells (IC 50 =15–30 μm). Workplace Institute of Experimental Botany Contact David Klier, knihovna@ueb.cas.cz, Tel.: 220 390 469 Year of Publishing 2018
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