Titanium(IV) carboxylate complexes: Synthesis,structural characterization and cytotoxic activity |
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Authors: | Santiago Gó mez-Ruiz,Beatriz Gallego,Željko Žižak,Evamarie Hey-Hawkins,Zorica D. Juranić,Goran N. Kaluđerović |
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Affiliation: | 1. Departamento de Química Inorgánica y Analítica, E.S.C.E.T., Universidad Rey Juan Carlos, 28933 Móstoles, Madrid, Spain;2. Institut für Anorganische Chemie der Universität Leipzig, Johannisallee 29, D-04103 Leipzig, Germany;3. Institute of Oncology and Radiology of Serbia, 11000 Belgrade, Serbia;4. Institut für Chemie, Martin-Luther-Universität Halle-Wittenberg, Kurt-Mothes-Straße 2, D-06120 Halle, Germany;5. Department of Chemistry, Institute of Chemistry, Technology and Metallurgy, University of Belgrade, Studentski trg 14, 11000 Belgrade, Serbia |
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Abstract: | Four titanium(IV) carboxylate complexes [Ti(η5-C5H5)2(O2CCH2SMes)2] (1), [Ti(η5-C5H4Me)2(O2CCH2SMes)2] (2), [Ti(η5-C5H5)(η5-C5H4SiMe3)(O2CCH2SMes)2] (3) and [Ti(η5-C5Me5)(O2CCH2SMes)3] (4; Mes = 2,4,6-Me3C6H2) have been synthesised by the reaction of the corresponding titanium derivatives [Ti(η5-C5H5)2Cl2], [Ti(η5-C5H4Me)2Cl2], [Ti(η5-C5H5)(η5-C5H4SiMe3)Cl2] and [Ti(η5-C5Me5)Cl3] and two (for 1–3) or three (for 4) equivalents of mesitylthioacetic acid. Complexes 1–4 have been characterized by spectroscopic methods and the molecular structure of the complexes 1, 2 and 4 have been determined by X-ray diffraction studies. The cytotoxic activity of 1–4 was tested against tumor cell lines human adenocarcinoma HeLa, human myelogenous leukemia K562, human malignant melanoma Fem-x, and normal immunocompetent cells, that is peripheral blood mononuclear cells PBMC and compared with those of the reference complexes [Ti(η5-C5H5)2Cl2] (R1), [Ti(η5-C5H4Me)2Cl2] (R2), [Ti(η5-C5H5)(η5-C5H4SiMe3)Cl2] (R3) and cisplatin. In all cases, the cytotoxic activity of the carboxylate derivatives was higher than that of their corresponding dichloride analogues, indicating a positive effect of the carboxylato ligand on the final anticancer activity. Complexes 1–4 are more active against K562 (IC50 values from 72.2 to 87.9 μM) than against HeLa (IC50 values from 107.2 to 142.2 μM) and Fem-x cells (IC50 values from 90.2 to 191.4 μM). |
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Keywords: | Anticancer drugs Titanocene complexes Cytotoxic activity Carboxylato ligands |
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