Synthesis and cytotoxicity studies of novel anion-exchanged Titanocene Y derivatives

Starting from the potential anticancer drug candidate Titanocene Y {bis-[(4-methoxybenzyl)cyclopentadienyl]titanium(IV) dichloride}, anion exchange experiments were performed using silver malonate (1a) or silver cyclobutane-1,1-malonate (1b) in order to yield bis-[(4-methoxy-benzyl)cyclopentadienyl]titanium(IV) malonate (2a) and bis-[(4-methoxy-benzyl) cyclopentadienyl]titanium(IV) cyclobutane-1,1-malonate (2b). In addition, Titanocene Y was reacted with salicylic acid (3a) or 3,5-dinitro-salicylic acid (3b) in the presence of diethylamine to synthesize bis-[(4-methoxy-benzyl)cyclopentadienyl]titanium( IV) salicylate (4a) or bis-[(4-methoxy-benzyl)cyclopentadienyl]titanium(IV) 3,5-dinitro-salicylate (4b). These titanocenes had their cytotoxicity investigated through preliminary in vitro testing on the LLC-PK (pig kidney epithelial) cell line in an MTT-based assay in order to determine their IC50 values. Titanocenes 2a-b and 4a were found to have IC50 values of 74 (+/- 13) mu M, 18 (+/- 5) mu M and 49 (+/- 11) mu M on the LLC-PK cell line, while compound 4b was found to have lost all its cytotoxic activity on this cell line. Copyright (C) 2010 John Wiley & Sons, Ltd.