We tested cytotoxicity of aminoferrocene-based prodrugs towards human androgen-responsive and unresponsive prostate cancer cell lines LNCaP and DU-145 correspondingly. Two prodrugs were selected, which are both activated at elevated concentrations of ROS with generation of quinone methide (antioxidant system inhibitor) and iron-containing compounds (N-benzylaminoferrocene (prodrug 1) and Fe salts (2)).
We observed that only prodrug 1 is active against the selected prostate cancer cells (IC50=11-27μM) and its activity correlates with the high cell-membrane permeability and increased production of intracellular ROS.
Bioorganic & medicinal chemistry letters. 2015 Jul 11 [Epub]
Margot Schikora, Alexander Reznikov, Liudmila Chaykovskaya, Olga Sachinska, Lubov Polyakova, Andriy Mokhir
Friedrich-Alexander-University of Erlangen-Nürnberg, Department of Chemistry and Pharmacy, Organic Chemistry Chair II, Henkestr. 42, 91054 Erlangen, Germany. , V. P. Komisarenko Institute of Endocrinology and Metabolism, National Academy of Medical Sciences of Ukraine, Kyiv, Ukraine. , V. P. Komisarenko Institute of Endocrinology and Metabolism, National Academy of Medical Sciences of Ukraine, Kyiv, Ukraine. , V. P. Komisarenko Institute of Endocrinology and Metabolism, National Academy of Medical Sciences of Ukraine, Kyiv, Ukraine. , V. P. Komisarenko Institute of Endocrinology and Metabolism, National Academy of Medical Sciences of Ukraine, Kyiv, Ukraine. , Friedrich-Alexander-University of Erlangen-Nürnberg, Department of Chemistry and Pharmacy, Organic Chemistry Chair II, Henkestr. 42, 91054 Erlangen, Germany.