Journal
JOURNAL OF MEDICINAL CHEMISTRY
Volume 56, Issue 17, Pages 6935-6944Publisher
AMER CHEMICAL SOC
DOI: 10.1021/jm400754c
Keywords
-
Categories
Funding
- Ruprecht-Karls-University of Heidelberg
- Friedrich-Alexander-University of Erlangen-Nurnberg
Ask authors/readers for more resources
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 (IC50) of the prodrugs toward human promyelocytic leukemia cells (HL-60) from 52 to 12 mu M. Finally, we demonstrated that the prodrugs are active against primary chronic lymphocytic leukemia (CLL) cells, with the, best compounds exhibiting an IC50 value of 1.5 mu M. The most active compounds were found to not affect mononuclear cells and representative bacterial cells.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available