Aminoferrocene-based prodrugs and their effects on human normal and cancer cells as well as bacterial cells

Marzenell P, Hagen H, Sellner L, Zenz T, Grinyte R, Pavlov V, Daum S, Mokhir A (2013)

Publication Type: Journal article, Original article

Publication year: 2013

Journal

Journal of Medicinal Chemistry American Chemical Society

Original Authors: Marzenell P., Hagen H., Sellner L., Zenz T., Grinyte R., Pavlov V., Daum S., Mokhir A.

Publisher: American Chemical Society

Book Volume: 56

Pages Range: 6935-6944

Journal Issue: 17

DOI: 10.1021/jm400754c

Abstract

Aminoferrocene-based prodrugs are activated under cancer-specific conditions (high concentration of reactive oxygen species, ROS) with the formation of glutathione scavengers (p-quinone methide) and ROS-generating iron complexes. Herein, we explored three structural modifications of these prodrugs in an attempt to improve their properties: (a) the attachment of a -COOH function to the ferrocene fragment leads to the improvement of water solubility and reactivity in vitro but also decreases cell-membrane permeability and biological activity, (b) the alkylation of the N-benzyl residue does not show any significant affect, and (c) the attachment of the second arylboronic acid fragment improves the toxicity (IC) of the prodrugs toward human promyelocytic leukemia cells (HL-60) from 52 to 12 μM. Finally, we demonstrated that the prodrugs are active against primary chronic lymphocytic leukemia (CLL) cells, with the best compounds exhibiting an IC value of 1.5 μM. The most active compounds were found to not affect mononuclear cells and representative bacterial cells. © 2013 American Chemical Society.

Authors with CRIS profile

Steffen Daum Lehrstuhl für Organische Chemie II Andriy Mokhir Professur für Organische Chemie

Involved external institutions

Deutsches Krebsforschungszentrum (DKFZ) DE Germany (DE) CIC biomaGUNE (Centro de Investigación Cooperativa en Biomateriales) ES Spain (ES)

How to cite

APA:

Marzenell, P., Hagen, H., Sellner, L., Zenz, T., Grinyte, R., Pavlov, V.,... Mokhir, A. (2013). Aminoferrocene-based prodrugs and their effects on human normal and cancer cells as well as bacterial cells. Journal of Medicinal Chemistry, 56(17), 6935-6944. https://dx.doi.org/10.1021/jm400754c

MLA:

Marzenell, Paul, et al. "Aminoferrocene-based prodrugs and their effects on human normal and cancer cells as well as bacterial cells." Journal of Medicinal Chemistry 56.17 (2013): 6935-6944.

BibTeX: Download