Novel zirconocene anticancer drugs?

From the reaction of Super Hydride (LiBEt3H) with 6-(4-methoxyphenyl) fulvene (1a), 6-(2-fluoro-4-methoxyphenyl) fulvene (1b), and 6-(4-N,N-dimethylaminophenyl) fulvene (1c) lithiated cyclopentadienide intermediates (2a–c) were synthesised. These intermediates were then transmetallated to zirconium with ZrCl4 to give benzyl-substituted zirconocenes bis-[(4-methoxybenzyl)cyclopentadienyl] zirconium(IV) dichloride (3a), bis-[(2-fluoro-4-methoxybenzyl)cyclopentadienyl] zirconium(IV) dichloride (3b) and bis-[(4-N,N-dimethylaminobenzyl)cyclopentadienyl] zirconium(IV) dichloride (3c). All three zirconocenes were characterised by single crystal X-ray diffraction and preliminary in vitro cell tests were performed with the zirconocene derivatives on the LLC-PK cell line in order to determine their cytotoxicity. Zirconocenes 3b and 3c did not show cytotoxicity up to a concentration of 170 μM, while 3a exhibited an IC50 value of 57 μM against LLC-PK.