Structure-property and structure-activity relationships of phenylferrocene derivatives as androgen receptor antagonists.

ABSTRACT

Ferrocene is a representative organometallic compound having a sandwich structure with high stability and hydrophobicity. In this study, we determined the physicochemical properties of a series of nitro- and cyanophenylferrocenes, and evaluated their biological activity as androgen receptor (AR) antagonists. Ferrocene derivatives exhibited hydrophobicity parameter π values in the range between 2.54 and 3.23, depending on the substituents, indicating that the hydrophobicity of ferrocene is suitable for its application as a hydrophobic core structure of nuclear receptor ligands. The synthesized ferrocene derivatives showed AR-antagonistic activity, and among them, 3-nitrophenylferrocene 14 exhibited the most potent activity with an IC50 value of 0.28 µM. The developed compounds may be candidates for further structural development as AR antagonists. These findings also support the utility of organometallic species as structural options for drug discovery.