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β-Diketonate Titanium Compounds Exhibiting High In Vitro Activity and Specific DNA Base Binding

Lord, Rianne M, Crossley, Benjamin D., Hebden, Andrew J., McMullon, Max W., Fisher, Julie, Phillips, Roger M. and McGowan, Patrick C. (2016) β-Diketonate Titanium Compounds Exhibiting High In Vitro Activity and Specific DNA Base Binding. ChemistrySelect, 1 (20). pp. 6598-6605. ISSN 2365-6549

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Abstract

Herein, we report 30 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 tumor 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.

Item Type: Article
Subjects: R Medicine > RM Therapeutics. Pharmacology
Schools: School of Applied Sciences
Related URLs:
Depositing User: Roger Phillips
Date Deposited: 10 Jan 2017 10:53
Last Modified: 10 Jan 2017 10:53
URI: http://eprints.hud.ac.uk/id/eprint/30783

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