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β-Diketonate Titanium Compounds Exhibiting High In Vitro Activity and Specific DNA Base BindingLord, Rianne M., Mannion, J.J., Crossley, B.D., Hebden, A.J., McMullon, M.W., Fisher, J., Phillips, Roger M., McGowan, P.C. 23 November 2016 (has links)
Yes / Herein, we report 31 new β-diketonate titanium
compounds of the type [Ti(O,O)2X2], whereby O,O = asymmetric or
symmetric β-diketonate ligand and X = Cl, Br, OEt or OiPr. Thirteen
new crystal structures are discussed and show that these octahedral
species all adopt cis geometries in the solid state. These compounds
have been tested for their cytotoxicity using SRB and MTT assays,
showing several of the compounds are as potent as cisplatin against
a range of tumour cell lines. Results also show the [Ti(O,O)2Br2]
complexes are more potent than [Ti(O,O)2Cl2], [Ti(O,O)2(OEt)2] and
[Ti(O,O)2(OiPr)2]. Using a simple symmetrical heptane-3,5-dione
(O,O) ligand bound to titanium, we observed more than a 50-fold
increase in potency with the [Ti(O,O)2Br2] (28) when compared to
[Ti(O,O)2Cl2] (27). One of the more potent compounds (6) has been
added to three different sixmers of DNA, in order to analyse the
potential DNA binding of the compound. NMR studies have been
carried out on the compounds, in order to understand the structural
properties and the species formed in solution during the in vitro cell
assays.
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