Aminoferrocene-based prodrugs activated by reactive oxygen species
Hagen H, Marzenell P, Jentzsch E, Wenz F, Veldwijk MR, Mokhir A (2012)
Publication Type: Journal article, Original article
Publication year: 2012
Journal
Original Authors: Hagen H., Marzenell P., Jentzsch E., Wenz F., Veldwijk M.R., Mokhir A.
Publisher: American Chemical Society
Book Volume: 55
Pages Range: 924-934
Journal Issue: 2
DOI: 10.1021/jm2014937
Abstract
Cancer cells generally generate higher amounts of reactive oxygen species than normal cells. On the basis of this difference, prodrugs have been developed (e.g., hydroxyferrocifen), which remain inactive in normal cells, but become activated in cancer cells. In this work we describe novel aminoferrocene-based prodrugs, which, in contrast to hydroxyferrocifen, after activation form not only quinone methides (QMs), but also catalysts (iron or ferrocenium ions). The released products act in a concerted fashion. In particular, QMs alkylate glutathione, thereby inhibiting the antioxidative system of the cell, whereas the iron species induce catalytic generation of hydroxyl radicals. Since the catalysts are formed as products of the activation reaction, it proceeds autocatalytically. The most potent prodrug described here is toxic toward cancer cells (human promyelocytic leukemia (HL-60), IC = 9 μM, and human glioblastoma-astrocytoma (U373), IC = 25 μM), but not toxic (up to 100 μM) toward representative nonmalignant cells (fibroblasts). © 2011 American Chemical Society.
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Germany (DE)How to cite
APA:
Hagen, H., Marzenell, P., Jentzsch, E., Wenz, F., Veldwijk, M.R., & Mokhir, A. (2012). Aminoferrocene-based prodrugs activated by reactive oxygen species. Journal of Medicinal Chemistry, 55(2), 924-934. https://doi.org/10.1021/jm2014937
MLA:
Hagen, Helen, et al. "Aminoferrocene-based prodrugs activated by reactive oxygen species." Journal of Medicinal Chemistry 55.2 (2012): 924-934.
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