Synthesis, characterization, biological studies and in vitro cytotoxicity on human cancer cell lines of titanium(IV) and tin(IV) derivatives with the α,α′‐dimercapto‐o‐xylene ligand

Abstract

The reaction of α,α′‐dimercapto‐o‐xylene (H2dmox) with different precursors such as SnMe2Cl2, [Ti(η5‐C5H5)2Cl2] and [Ti(η5‐C5H4Me)2Cl2] (1:1) in the presence of two equivalents of NEt3 yielded the complexes [SnMe2(dmox)] (1), [Ti(η5‐C5H5)2(dmox)] (2) and [Ti(η5‐C5H4Me)2(dmox)] (3), respectively. 1–3 have been characterized by spectroscopic methods; in addition, complex 3 has been determined by X‐ray diffraction studies. Furthermore, structural studies based on density functional theory calculations of 1 and 2 have been carried out. The cytotoxic activity of 1–3 was tested against the tumour cell lines human adenocarcinoma HeLa, human myelogenous leukaemia K562 and human malignant melanoma Fem‐x. The results of this study show a higher cytotoxicity of the tin(IV) complex (1) in comparison to their titanium(IV) counterparts (2 and 3) as well as an improvement in the cytotoxic activity of compounds 2 and 3 compared to their titanocene(IV) dichloride analogues [Ti(η5‐C5H5)2Cl2] and [Ti(η5‐C5H4Me)2Cl2]. In view of the relatively high cytotoxicity of compound 1, a detailed study on the effects of the in vitro treatment of cancer cell lines using this compound was carried out. Thus cell cycle experiments on all the studied cell lines treated with 1 show that this complex seems to cause disturbances in the G1 phase of HeLa, and in the G1 and G2/M phases of Fem‐x cell line, while almost no disturbances were observed in the cycle of K562 cells treated with 1. Finally, DNA laddering method showed that treatment of the HeLa and Fem‐x cell lines with IC90 doses of 1 resulted in the induction of apoptosis. Copyright © 2012 John Wiley & Sons, Ltd.