Hydrogen Peroxide-Responsive Aminoferrocene Prodrugs

Körber M, Rühle J, Halter F, Mokhir A (2025)

Publication Type: Journal article

Publication year: 2025

Journal

DOI: 10.1002/ejoc.202500294

Abstract

Aminoferrocene (AF)-based prodrugs are activated in cancer cells through reactions with H2O2 and other reactive oxygen species (ROS), generating electron-rich AF's. These, in turn, induce the production of highly toxic O2⁻ and HO·, leading to cancer cell death. Effective activation of these prodrugs depends on their ability to target intracellular organelles rich in ROS, as nontargeted prodrugs are practically inactive. In this study, the boronic acid pinacol ester—previously used as a ROS-trigger—is replaced with an α-ketoamide fragment, which is more selective and sensitive to H2O2. This modification enhances the anticancer efficacy of untargeted AF prodrugs, reducing the IC50 from 23.9–35.5 μM (previously reported prodrug 13b) to 5–6.4 μM (new prodrug 2a) in human ovarian cancer A2780 and Burkitt's lymphoma BL-2 cells. Further analysis confirms that the anticancer effect of 2a is driven by its ability to markedly increase intracellular ROS levels in both the cytoplasm and mitochondria.

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How to cite

APA:

Körber, M., Rühle, J., Halter, F., & Mokhir, A. (2025). Hydrogen Peroxide-Responsive Aminoferrocene Prodrugs. European Journal of Organic Chemistry. https://doi.org/10.1002/ejoc.202500294

MLA:

Körber, Marlies, et al. "Hydrogen Peroxide-Responsive Aminoferrocene Prodrugs." European Journal of Organic Chemistry (2025).

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