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

In 2008, researchers synthesized the first organometallic complexes derived from the nonsteroidal antiandrogen nilutamide, with a ferrocenyl substituent. The N-substituted complexes had a weak or moderate antiproliferative effect (IC50 around 68 μM) on hormone-dependent and -independent prostate cancer cells. However, the C(5)-substituted compounds showed toxicity levels 10 times higher (IC50 around 5.4 µM), likely due to a structural effect linked to the aromatic character of the ferrocene. This effect seemed connected to a cytotoxic effect rather than an antihormonal one. The study suggested a new family of molecules that could be active against both hormone-dependent and hormone-independent prostate cancer cells.