Redox-dependent cytotoxicity of ferrocene derivatives and ROS-activated prodrugs based on ferrocenyliminoboronates

Abstract

Four ferrocene derivatives - ferrocenecarboxylic acid, ferrocenium salt, ferroceneboronic acid, and aminoferrocene - were characterized electrochemically, and their cytotoxicity was probed using cancer cells (line MG-63). We related the observed cytotoxicity with the determined redox potentials of these four ferrocenes - aminoferrocene with its lowest redox potential exhibited the highest cytotoxicity. Thus, we synthesized four derivatives consisting of aminoferrocene and phenylboronic acid residue with the intent to employ them as ROS-activated prodrugs (ROS - reactive oxygen species). We characterized them and studied their time-dependent stability in aqueous environments. Then, we performed electrochemical measurements at oxidative conditions to confirm ROS-responsivity of the synthesized molecules. Finally, the cytotoxicity of the synthesized molecules was tested using cancer MG-63 cells and noncancerous NIH-3T3 cells. The experiments revealed sought behaviour, especially for para-regioisomers of synthesized ferrocenyliminoboronates.

Keywords: Aminoferrocene; Electrochemical characterization; Ferrocenyliminoboronates; MG-63; ROS-activated prodrugs; Redox-dependent cytotoxicity.