Synthesis and Structure–Activity Relationships of the First Ferrocenyl-Aryl-Hydantoin Derivatives of the Nonsteroidal Antiandrogen Nilutamide Academic Article uri icon

  •  
  • Overview
  •  
  • Research
  •  
  • Identity
  •  
  • Additional Document Info
  •  
  • View All
  •  

abstract

  • We present here the first synthesis of organometallic complexes derived from the nonsteroidal antiandrogen nilutamide, bearing a ferrocenyl substituent at position N(1) or at C(5) of the hydantoin ring; for comparison, we also describe the C(5) p-anisyl organic analogue. All of these complexes retain a modest affinity for the androgen receptor. The N-substituted complexes show a weak or moderate antiproliferative effect (IC 50 around 68 microM) on hormone-dependent and -independent prostate cancer cells, while the C(5)-substituted compounds exhibit toxicity levels 10 times higher (IC 50 around 5.4 microM). This strong antiproliferative effect is probably due to a structural effect linked to the aromatic character of the ferrocene rather than to its organometallic feature. In addition, it seems connected to a cytotoxic effect rather than an antihormonal one. These results open the way toward a new family of molecules that are active against both hormone-dependent and hormone-independent prostate cancer cells.

authors

  • Mcglinchey, Michael James
  • Payen, Olivier
  • Top, Siden
  • Vessières, Anne
  • Brulé, Emilie
  • Plamont, Marie-Aude
  • J. McGlinchey, Michael
  • Müller-Bunz, Helge
  • Jaouen, Gérard

publication date

  • March 2008

has subject area