Pseudo-halide derivatives of titanoceneY: synthesis and cytotoxicity studies

Abstract

The well-known anticancer drug candidate bis-[(p-methoxybenzyl)cyclopentadienyl] titanium(IV) dichloride (TitanoceneY) was reacted with sodium azide or potassium cyanate, thiocyanate or selenocyanate in order to give pseudo-halide analogues 2a–d of TitanoceneY. 2b and 2c were characterised by single crystal X-ray diffraction, which confirmed the expected nitrogen binding of the cyanate and thiocyanate to the titanium centre. All four 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. Titanocenes2a–d were found to have IC50 values of 24 (±8) μM, 101 (±14) μM, 54 (±21) μM and 27 (±4) μM respectively. All four titanocene derivatives show significant cytotoxicity improvement when compared to unsubstituted titanocene dichloride and 2a and 2d showed similiar cytotoxic behaviour to TitanoceneYin vitro.