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Letters in Drug Design & Discovery

Editor-in-Chief

ISSN (Print): 1570-1808
ISSN (Online): 1875-628X

The Cytotoxicity of Titanocene Y Against CAKI-1 Cells: An In Vitro Formulation Study

Author(s): Megan Hogan, Brendan Gleeson and Matthias Tacke

Volume 7, Issue 5, 2010

Page: [310 - 317] Pages: 8

DOI: 10.2174/157018010791163479

Price: $65

Abstract

Various formulations containing titanocene Y (bis-[(p-methoxybenzyl)cyclopentadienyl] titanium (IV) dichloride) were prepared and tested in vitro on CAKI-1 cells in order to compare the cytotoxic behaviour of the compound with different formulation reagents. Formulations were prepared with non-ionic surfactants like Cremophor EL and Tween 80, pegylated reagents PEG-400 and Solutol HS 15, and the co-solvent Soluphor P (pyrrolidone-2). All formulations were tested with and without the presence of dimethylsulfoxide. When the lipophilic derivative titanocene Y was formulated with Soluphor P and tested in vitro, an IC50 value of 10 (+/- 1) μM was observed, which is a 3-fold increase in cytotoxicity when compared to the DMSO formulation. In order to compare to a more hydrophilic titanocene this Soluphor P formulation method was extended to the water-soluble titanocene G, which is a dihydrochloride derivative of bis-[(1-methyl- 3-dimethylaminomethylindol-2-yl)cyclopentadienyl] titanium (IV) dichloride). When titanocene G was tested in vitro in the presence of Soluphor P, it resulted in a 10-fold increase in cytotoxicity with an IC50 value of 0.71 (+/- 0.24) ?μM against CAKI-1 cells.

Keywords: Titanocene Y, Formulation, CAKI-1 cells, Cremophor EL, Tween 80, PEG-400, Solutol HS 15, Soluphor P, Solubility, Cytotoxicity, MTT assay

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