Synthesis and biological activity of ferrocenyl derivatives of the non-steroidal antiandrogens flutamide and bicalutamide

A series of ferrocenyl derivatives of the two non steroidal antiandrogens flutamide and bicalutamide have been prepared. Ferrocenyl bicalutamide complexes were initially synthesized in their racemic forms, and subsequently prepared as pure (R) and (S) enantiomers, and their structure was determined by X-ray crystallography. Most of the complexes retain a modest affinity for the androgen receptor and show an antiproliferative effect on both hormone-dependent (LNCaP) and -independent (PC-3) prostate cancer cells. Ferrocenyl derivatives of bicalutamide are the most cytotoxic (IC50 values on PC-3 around 15 μM); however, they are less potent than the ferrocenyl derivatives of ethynyltestosterone or nilutamide (IC50 around 5 μM).

Graphical abstractFerrocenyl derivatives of flutamide (1–3) and bicalutamide (4–5) were prepared. In the case of 5, the complex was first prepared in its racemic form and then as pure (R) and (S) enantiomers. The structure of 4 was determined by X-ray crystallography. Complexes of bicalutamide 4 and 5 showed a significant cytotoxic effect on prostate cancer cells (IC50 values on PC-3 around 15 μM).Figure optionsDownload full-size imageDownload as PowerPoint slideResearch highlights► Synthesis of ferrocenyl derivatives of flutamide and bicalutamide. ► Compounds were tested against LNCaP and PC-3 prostate cancer cells. ► Significant antiproliferative activities have been found.