Novel benzyl-substituted vanadocene anticancer drugs

From the reaction of 6-(p-methoxyphenyl) fulvene (1a), 6-(3,4-dimethoxyphenyl) fulvene (1b) and 6( 3,4,5-trimethoxyphenyl) fulvene (1c) with LiBEt3H, lithiated cyclopentadienide intermediates (2a-c) were synthesised. These intermediates were then transmetallated to vanadium with VCl4 to yield the benzyl-substituted vanadocenes bis-[(p-methoxybenzyl) cyclopentadienyl] vanadium(IV) dichloride (3a), bis-[(3,4-dimethoxybenzyl) cyclopentadienyl] vanadium(IV) dichloride (3b), and bis-[(3,4,5-trimethoxybenzyl) cyclopentadienyl] vanadium(IV) dichloride (3c). The two vanadocenes 3a and 3c were characterised by single crystal X-ray diffraction. All three vanadocenes had their cytotoxicity investigated through MTT based preliminary in vitro testing on the LLC-PK (pig kidney epithelial) cell line in order to determine their IC50 values and compare them with the corresponding titanocene dichloride derivatives. Vanadocenes 3b-c were found to have IC50 values of 9.1 and 8.3 mu M, while 3a showed a superior value of 3.0 mu M, respectively. (C) 2008 Elsevier B.V. All rights reserved.