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) µM , 18 ( ± 5) µM and 49 ( ± 11) µM on the LLC‐PK cell line, while compound 4b was found to have lost all its cytotoxic activity on this cell line. Copyright © 2010 John Wiley & Sons, Ltd.